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Acta Neurobiol. Exp. 1993,53: 265-291

POLISH NEUROSCIENCE SOCIETY

EUROPEAN BRAIN AND BEHAVIOUR SOCIETY

NENCKI INSTITUTE OF EXPERIMENTAL BIOLOGY POLISH ACADEMY OF SCIENCES

THE INTERNATIONAL WORKSHOP ON EMOTIONAL

AND MOTIVATIONAL MECHANISMS OF BEHAVIOUR:

NEUROBIOLOGICAL, PHARMACOLOGICAL AND

PSYCHOLOGICAL ASPECTS

Organizers : Adam FRqCZEK , Wojciech KOSTOWSKI, Jolanta ZAGRODZKA

Warsaw, October 13- 15, 1994

S T R A C T S

CONTENTS

I . General considerations: concepts. definitions and methodological aspects of the research on motivational behaviour in neurobiological. pharmacological and psychological perspective

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . BLANCHARD C .. Gender and emotion: animal studies 268

. . . . . . . CAPRARA G.V. . Motivation. emotion and cognition: towards integration into a personological perspective 268

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . FONBERG E .. Puzzles in motivation 269 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . WILLNER P .. A realistic animal model of depression 269

I1 . Aggression, fear and social behaviour (neuroanatomical and neurochemical substrates, psychosociological aspects)

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . BLANCHARD R.J. . Defensive behaviour and clinical psychopathology 270 . . . . . FRACZEK A .. Models of human aggression motivation: sociopsychological and developmental perspectives 270

. . . . . . . . . . . . . . KRSIAK M .. Aggression. fear and social behavior: neuropharmacological and ethological aspects 271 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . REYKOWSKI J .. Social motivation 271

. . . . . . . ROMANIUK A .. Correlation of neurochemical mechanisms and emotional-defensive behaviour in the cat 272

. . . . . . . ZAGRODZKA J .. The destruction of the dorsal noradrenergic system and its effects on fear in cats and rats 272 I11 . Mechanisms of drug and alcohol addiction (the role of limbic system, neurotransmission processes, psychosocial aspects) BIELAJEW C., TRZCINSKA M . and BUSHNIK T . . Characteristics of the substrates for stimulation-induced feedingandreward . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273 BRAIN P.F., KURISHINGAL H . and RESTALL C.J. . Lasting effects of prefrontal exposure to benzodiazepine agonists and antagonists on emotional behaviour and neural development in the mouse . . . . . . . . . . . . . . . . . . . . . . . . 274 MASSI M., CICCOCIOPPO R., POMPEI P . and PANOCKA I . . Why do 5HT2 antagonists not reduce alcohol intake in sardinian alcohol preferring (sP) rats genetically selected for high ethanol intake? . . . . . . . . . . . . . . . . . . . . . 274 OVERSTREET D.H. . Behavioural and pharmacological heterogeneity in alcohol-preferring rats . . . . . . . . . . . . . . . 275 PANOCKA I., CICCOCIOPPO R . and MASSI M . . Mechanisms of ethanol intake inhibition produced by the 5HT2 receptor antagonist ritanserin in rats non genetically selected for high ethanol preference . . . . . . . . . . . . . . . . . . . . . . . 275 PUCILOWSKI 0 .. Pharmacological perspective on calcium channel blockers for alcohol and drug addition . . . . . . . 276 SADOWSKI B . . Selective breeding of mice for high and low stress-induced analgesia: differentiation of opioid-mediatedphenomena . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277 TROJNIAR W .. Organization of the central system of food reward and its relevance for drug taking behaviour . . . . 277 IV . Motivation, emotions and cognition (neurobiological and psychological studies) BECK J .. Motivational mechanisms underlying sexual behaviour in rats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 278 KOFTA M . . Motivational deficit in learned helplessness: behaviour slow-down or decline of intrinsic motivation? . 278 KOWALSKA D.M. . Contributions of the temporal lobe structures and their connections to memory functions and emotionalbehaviour . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279 PISULA W .. Stimulus behaviour in rats . studies on individual differences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279 SAGVOLDEN T . . The level of motivation is important for the expression of hyperactivity in an animal model of attention-deficit hyperactivity disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 280 SOSNOWSKI T .. Tonic heart rate and demands: toward a motivational explanation . . . . . . . . . . . . . . . . . . . . . . . . . . 280 Posters BRUDZYNSKI S.M. and FU X.W . . Role of the cholinergic and glutaminergic transmission in the control of ultrasonic vocalization in the rat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281 CHIKADZE A .. Structural-functional organization of conditioned reflexes and delayed reactions in cats . . . . . . . . . . 281 DONAT P . and KRSIAK M .. The role of 5-HT in fear-related behaviour of male mice . . . . . . . . . . . . . . . . . . . . . . . . 282 JELEN P., SOLTYSIK S., ZAGRODZKA J . and KASICKI S . . Changes in the respiratory pattern as an indicator of fearinrats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283 JURKOWLANIEC E., ORZEL-GRYGLEWSKA J . and TROJNIAR W . . Sleep-waking pattern and motor activity after lateral hypothalamic damage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283

KACZMAREK B.L.J. - Aggression and frontal lobe deficits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 284 SEREDENIN S.B. and HALIKAS J.A. - Interactions between saccharin and alcohol . . . . . . . . . . . . . . . . . . . . . . . . . . 284 KLEJBOR I. and TROJNIAR W. - Facilitation of VTA stimulation-induced locomotor activity after contralateral VTAlesion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 284 KORZENIOWSKA A., KASICKI S. and ZAGRODZKA J. - Emotional state amygdala-accumbens information flow in freely moving rats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285 KOSTOWSKI W., DYR W. and JANKOWSKA E. - Studies on the effects of 5-HT-3 receptor antagonists in an animalmodelofethanoldependence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285 KROTEWICZ M. - Inhibitory influence of 6-hydroxydopamine administration into the hypothalamic paraventricular nucleus on carbohydrate intake in cats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 286 OSTROVSKAYA R., GUDASHEVA T.A., VORONINA T.A., GARIBOVA T., VALDMAN H., OVERSTREET D.H., SEREDENIN S. and HALIKAS J. - GVS-111, a novel cognitive enhancer with anxiolytic properties . . . . . . . . . . . . . 286 NAZAR M., STEFANSKI R., BIDZINSKI A., JESSA M. and PLAZNIK A. - The effect of serotonin depletion and intra-hippocampal midazolam on rat behaviour in the Vogel conflict test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287 SOKOLOWSKA B. and CZARKOWSKA-BAUCH J. - Behavioural modulation of excitability of a-motoneurons of thesoleusmuscleinrats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287 GODZINSKA E.J. and SZCZUKA A. - The effect of group size on response to animal prey in workers of the wood ant Formica Polycteiza Forst kept in queenless and broodless groups . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 288 STASZEWSKA M. and TROJNIAR W. - Involvement of the anterodorsal thalamic nuclei in feeding induced by stimulation of the ventral tegmental area . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 288 STRZELCZUK M. and ROMANIUK A. - Neurochemical basis of the fear reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . 289 TRZCINSKA M. and BIELAJEW C. - In search of the forebrain reward substrate: a caudate-putamen and medial prefrontalcortexmappingstudy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289 WALASEK G., WESIERSKA M. and ZIELINSKI K. - Stimulus modality effects on forward and on backward CER conditioning in rats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 290 WERKA T. - Post-stress analgesic reactivity in rats with partial amygdala lesion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 290 WIECZOREK M. and ROMANIUK A. - The role of the noradrenergic systems in the regulation of the post-carbachol emotional-defensive reaction in cat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291

268 General considerations

I. GENERAL CONSIDERATIONS: CONCEPTS, DEFINITIONS AND METHODOLOGICAL ASPECTS OF THE RESEARCH ON MOTIVATIONAL BEHAVIOUR IN NEUROBIOLOGICAL, PHARMACOLOGICAL AND PSYCHOLOGICAL PERSPECTIVE

GENDER AND EMOTION: ANIMAL STUDIES Caroline Blanchard Pacific Biochemical Research Center and Department of Anatomy,University of Biomedical Research Center and Department of Anatomy, University of Hawaii, Honolulu, HI 96822, USA Across countries and cultures, women are approximately twice as likely as men to suffer from depress-

ion. Many anxiety disorders, such as simple phobia, panic with agoraphobia, and post-traumatic stress disorder, are also overrepresented among women. Although there may be gender effects on rates of reporting or seeking treatment for such disorders, or on personal experience of highly stressful events, these differences alone cannot account for the much higher rates of emotion-related disorders among women. An alternative view is that females differ in some systematic neurobehavioral system or systems involved in these psychopathologies. Female rats consistently show a pattern of differences in defensive behaviours, compared to males, that parallel the effects of exposure to a nonpainful threat stimulus (cat or cat odor) in the same tests and measures. These indications of greater defensiveness for females are particularly common in situations involving potential, as opposed to actual and present, threat. Also, pharmacological studies indicate sex differences in the effects of selective serotonin receptor agonist on defensive responding. This array of findings indicates that sex differences must be considered in studies of the pharmacological control of defensive behaviours, and suggests that responsivity to sex effects may be an additional criterion for the suitability of animal models of anxiety. Finally, they are consonant with the view that female overrepresentation in emotional psychopathology may have, in part, a biological basis.

Supported by NIH MH42803 and RR03061 and by NSF NBS91111524.

MOTIVATION, EMOTION AND COGNITION: TOWARDS INTEGRATION INTO A PERSONOLOGICAL PERSPECTIVE Gian Vittorio Caprara Dipartimento di Psicologia, Universita Degli Studi di Roma " La Sapienza", Via dei Marsi 78, Roma, Italy Research on complex human motivations is strictly intertwined with the study of emotion and cogni-

tion. Motivation should be considered a higher order construct than emotion and cognition in that it refers to forms of psychic organization resulting from emotional and cognitive components. The study of motivation concerns what triggers, maintains, intensifies, interrupts or alters the various tendencies toward action. It implies the study of mechanisms that lead to the decision of which goals to pursue as well as the study of mechanisms that sustain over time the efforts that are needed to achieve the selected goals. Motivation integrates emotions and cognition at a more complex level of organization. Each motivational system deserves special attention with regard to the structures, processes and mechanisms which accom- pany and determine its development, functioning and transformations. Consequently it is likely that a psychology of motivations (plural) will be more appropriate than a psychology of motivation to enlighten the

General considerations 269

specificity of each system of motives and the specificity of the various systems of emotions and of cognition from which it derives and which it integrates. To capture the subtle links and the multiple relationships among various motivations the study of personality place into a higher order organization the entire flow of conduct which results from the combination or alternation of motivations.

PUZZLES IN MOTIVATION Elzbieta Fonberg Department of Neurophysiology, Nencki Institute of Experimental Biology, 3 Pasteur St., 02-093 Warsaw, Poland The concept of motivation is not unitary. The problem of motivation originated in psychology and was

only later adopted by physiologists. The mechanisms underlying motivational processes are differently understood by various researchers and there is some overlap with the concept of drive or arousal. Thus, the term "motivation" is used by particular authors in different senses, what results in numerous discrepancies and misunderstandings. There are also severe discrepancies concerning the physiological (in the broad sense, including metabolic fluctuations), neurophysiological, neuroanatomical and biochemical bases of motivation. The theory stressing the crucial role of the hypothalamus presented by Stellar (1954) has since been criticized. Several other theories as well as controversial research data related to above problems, will be discussed. Cognitive versus emotional triggers for motivation will be analyzed as well. Re- ward and punishment as the incentives for motivation, and their relations to learning, have not yet been clearly elucidated. Evidence of the shift between reward and punishment reveal the chink in the unitary concept of reward. The nature of reward's, physiological and biochemical mechanisms are also controversial. In this respect the problem arises as to how the pathological aspects of behavior and learning are linked with the mechanisms of motivation. Numerous experimental data reported every year add to this puzzle. Our own results, to which I will refer, address some of these problems, but complicated others.

A REALISTIC ANIMAL MODEL OF DEPRESSION Paul Willner Department of Psychology, University of Wales, Swansea, SA2 8PP, UK Inferences drawn from an animal model of psychopathology are valid only to the extent that the model

itself is valid. The chronic mild stress (CMS) model of depression will be used to illustrate three different approaches to validating an animal model: predictive validity, face validity and construct validity. In the CMS model, chronic exposure of rats or mice to a sequence of mild stressors decreases responsiveness to rewards (anhedonia). Studies will be reviewed showing that CMS induced anhedonia: ( I ) cannot be ex- plained by nonspecific effects (eg. changes in fluid balance) and is independent of the method of evaluating responsiveness to rewards (construct validity); (2) is accompanied by a variety of other changes characteristic of depression, including decreased REM-sleep latency (face validity); (3) is reversed by chronic (but not acute) treatment with antidepressants of various classes, but not by non-antidepressants [ predictive validity]. Both behavioural (eg. place conditioning) and biochemical (receptor binding) data suggested that CMS-induced anhedonia reflects a decrease in the sensitivity of dopamine D2D3 receptors in the ventral striaturn. Conversely, effective drug treatments of CMSs may represent a final common pathway ir- respective of the primary site and mechanism of antidepressant drug action.

270 Aggression, fear and social behaviour

11. AGGRESSION, FEAR AND SOCIAL BEHAVIOUR (NEUROANATOMICAL AND NEUROCHEMICAL SUBSTRATES, PSYCHOSOCIOLOGICAL ASPECTS)

DEFENSIVE BEHAVIOUR AND CLINICAL PSYCHOPATHOLOGY Robert J. Blanchard Department of Psychology and Bekesy Laboratory of Neurobiology, University of Hawaii, Honolulu, HI 96822, USA Test situations involving "natural" threat stimuli such as attacking conspecific orpredators, or situations

or stimuli associated with these, enable analysis of drug effects on particular defensive behaviours including flight, spatial avoidance, freezing, defensive threat and attack, and risk assessment. Paradigms pola- rizing these behaviours through manipulation of test situations and test stimuli provide a thorough and precise methodology for analysis of the effects of drugs on defense. Data on the effects of a variety of psychoactive compounds indicate that administration of clinically effective anxiolytic drugs selectively alters an "anxiolytic profile" of four specific measures particularly associated with reactivity to potential threat. The same behaviours are altered in response to chlordiazepoxide in a mouse test battery. As the "anxiolytic profile" was first obtained in rats, this provides evidence of across-species generality of these effects. In contrast, the panicogenic drug yohimbine and chronic administration of alprazolam, which is effective against panic attack, alter flightJescape behaviours. These are not part of the "anxiolytic profile". These findings suggest that the patterning of drug effects on defensive behaviours may be related to their action on the target symptoms for a variety of defensive psychopathologies. Finally, recent studies suggest that the parameters of both behavioural and physiological change following chronic social stress may respond to individual difference factors involving defensiveness. These studies suggest considerable homo- logy between the defensive behaviours of lower mammals, and emotion-linked human psychopathology.

Supported by NIH MH42803 and RR0306 1.

MODELS OF HUMAN AGGRESSION MOTIVATION: SOCIOPSYCHOLOGICAL AND DEVELOPMENTAL PERSPECTIVES Adam Frqczek Institute of Psychology, Polish Academy of Sciences, 61 Podleina St., 01-673 Warsaw, Poland It is commonly accepted that the causal factors underlying specific aggressive and hostile acts among

people are diverse and complex. Aggression and hostility refers to behaviours more or less intentionally organized in such a way that it leads to harm, loss of someone's values or suffering and pain in those against whom the behaviour is directed. Developmentally, primary aggressive responses which emerge very early in ontogenesis are the natural reactions to noxious stimuli. Also, relatively early in the development of the child there emerge behaviours which serve for protection or the acquisition of attractive objects and maintenance of emotional satisfactory relationships. Due to socialization experiences these two prototypes are transformed into aggressivekostile behaviours which are reactive-emotogenic vs. aggressivefhostile acts which are instrumentaVtask oriented. Both simple aggressive responses and organized aggressivekostile behaviors can lead to outcomes that are beneficial, emotionally and/or materially, to the subject. This is a pathway for the development of an autonomous, "inherent" need to aggreess, i.e., to be aggressive and hostile for pleasure. Developing children also acquire specific beliefs about themselves and the others. They learn moral and social norms, and they acquire goals and values. Violence and destruction against other people can be, par excellance, a realization of the individual's life orientations and goals, i.e., nor-

Aggression, fear and social behaviour 271

mativelgoal oriented aggression and hostility. Thus, interpersonal aggression and hostility differ not only with respect to their manifestations but also specific forms are based on various categories of intrapsychic regulatory mechanisms formed during socialization.

AGGRESSION, FEAR AND SOCIAL BEHAVIOUR: NEUROPHARMACOLOGICAL AND ETHOLOGICAL ASPECTS MiloS KrSiak Department of Pharmacology, 3rd Faculty of Medicine, Charles University, 87 Ruska St., 100 00 Prague 10, Czech Republic The aim of this paper is to demonstrate the potential of a pharmacological and ethological approach to

understanding aggression, fear and social behaviour. 1. Drugs as tools in the study of the molecular mechanisms of aggression and fear: in an ethologically

based behavioural model some mice are predominantly aggressive while others are predominantly timid (exhibit escapes or defensive postures even though their partners are non-aggressive). We wondered whether there is a drug which would be able to eliminate aggressive or defensive-escape activities in mice without inhibiting their locomotion or producing other adverse effects (assuming that such a drug could be a marker of the key molecular mechanism of aggression or fear). To answer this question, we analyzed our database containing data on the effects of 76 drugs from various pharmacological classes tested in wide dose ranges in aggressive and timid mice under a uniform procedure in our laboratories during the last 21 years (1,2). Although some drugs completely inhibited attacks without reducing locomotion, none of the 76 drugs tested was able to inhibit timid activities ( escape or defenses) totally at non sedative doses. Even the most effective well-established anxiolytic drugs were able to reduce timid activities only par- tially. Thus it seems that the present axiolytic drugs do not hit the key mechanisms of anxiety (fear).

2. Individual approach: an inbred strain of rats that responds to a strong stress (a water immersion re- straint) predominantly with gastric lesion is much more aggressive in intraspecies conflict than another strain reacting to the same stress largely with heart lesion (measured by 2 0 3 ~ g incorporation).

3. Why is social stimulation more effective? Some emotions (e.g., sexual arousal, selfesteem) are stimulated much more effectively by others than by the self. Why is this so? How does this contribute to survival, (one of the core ethological questions)? An attempt will be made to answer this question.

1. KrSiak M.(1975) Brit.J.Pharmacol.55: 141-150. 2. KrSiak M.(1991) Neurosci.Biobehav.Rev.15: 439-445. Supported by Czech grants GAUK No.225, GACR No.307/93/1122 and IGA No.0865-3.

SOCIAL MOTIVATION Janusz Reykowski Institute of Psychology, Polish Academy of Sciences, 61 Podles'na St., 01-673 Warsaw, Poland Social motivation is considered by some authors as a "need to affiliate with other humans". Our analysis

suggests that what manifests itself as a "tendency toward sociability" is not a homogenous disposition (or trait, or need, or drive). A human being is attractive to another human being for a variety of reasons. In the first place, he or she is a source of stimuli that bring strong sensory and functional pleasure; this is a basis for the development of a strong demand for objects which possess such qualities. It can be argued that the difference in sensivity to such stimuli is affected by some biological factors, especially those which control the demand for stimulation (sensation seeking). Attractiveness of humans can also be related to the fact that some of them ( well-known, nurturing persons) can serve as a "device" for controlling stimulation - especially in an unfamiliar and threatening environment. The other mechanism of social motiva-

272 Aggression, fear and social behaviour

tion, uniquely human, is related to the fact that human beings play a critical role as a source of support for individual's system of meaning - they provide information necessary for the validation of personal beliefs, especially beliefs concerning the self. Inflow of information concerning individual beliefs seems to be as important for the existence of a cognitive system as food intake for an organism. Considering the fact that human beings can provide a great variety of satisfaction for an individual, it is hardly surprising that a tendency to associate with people, to care for them (as for anything that has value for an individual), to exploit them, to take advantage of them, or to abuse them should be (and really is) the most common event of a social life. But the value that an individual attaches to another human beings can be independent of their relation to hisfher personal needs or desires. It can originate from internalized normative systems or it can emerge as a result of the development of a cognitive representation of social world. The very fact of ordering social phenomena in a cognitive network leads to the value attribution to objects represented in the network. The process gives rise to a genuine prosocial motivation; that is, a motivation that is not controlled by anticipation of personal gain or avoiding personal loss but by gain or loss as affecting an external social object.

CORRELATION OF NEUROCHEMICAL MECHANISMS AND EMOTIONAL-DEFENSIVE BEHAVIOUR IN THE CAT Andrzej Romaniuk Department of Neurophysiology, University of M d i , 66 Rewolucji 1905r. St., 90-222 M d i , Poland The lecture will concern the following topics: (1) Several kinds of cat's emotional-defensive behaviour:

affective aggression, flight reaction and threat reaction. Autonomic and behavioral expression in offensive and defensive behaviour. (2) Carbachol-induced defensive response as an equivalent model of a cat's natural behaviour after being exposed to threat: the effects of experimental threatening or "neutral" stimuli on the post-carbachol emotional-defensive response. (3) Neurochemistry of aggressive behaviour: central triggering mechanisms of rage, serotonin depletion with p-chlorophenylalanine effects on carbachol-induced defensive behaviour and brain monoamine content. Participation of dorsal and median raphe nuclei and dorsal and ventral noradrenergic systems in the regulation of aggressive behaviour. Interactions of catecholaminergic and serotonergic systems in emotional brain areas in the regulation of aggressive behaviour. (4) Neurochemistry of flight reaction: central triggering mechanism of anxiety - cholinergic and/or GABA-ergic mediation? Interactions of catecholaminergic and serotonergic systems in emotional brain areas in the regulation of the flight reaction.

THE DESTRUCTION OF THE DORSAL NORADRENERGIC SYSTEM AND ITS EFFECTS ON FEAR IN CATS AND RATS Jolanta Zagrodzka Nencki Institute of Experimental Biology, 3 Pasteur St., 02-093 Warsaw, Poland The biochemical basis for fear reactions is still not fully understood. Among other neurotransmitter

pathways, the noradrenergic system has been implicated in the regulation of fear and anxiety. The aim of our experiments was to study the behavioural and biochemical effects of the destruction of the dorsal noradrenergic system on fear-related behaviours in cats and rats. The animals were tested in various social and stressogenic situations, which were able to evoke anxiety or defensive behaviour. After the behavioural profile of both partners in each pair was established, the submissive animals were treated with DSP-4, a highly selective neurotoxin that destroys noradrenergic neurons. It has been found that DSP-4 lesions do not change well established dominance order in cats competing for prey, unless the stresfull stimulus

Mechanisms of drug and alcohol addiction 273

(100 dB white noise) is presented during the predatory competition. This stimulus evokes a natural reaction of anxiety in intact cats, whereas DSP-4 lesioned animals attacked the mice, in spite of never having done this before in the presence of their "dominating" partners. Also, when tested in an open field with a novel object, DSP-4 cats explored significantly more than control animals. In DSP-4 treated rats a marked decrease of defensive episodes and an increase of offense episodes during social interactions in the resident- intruder paradigm were observed. DSP-4 rats explored more and spent more time in a highly illuminated (aversive) area than controls. It might be suggested that changes in social behaviour as well as in reactions to stressful stimuli are due to fear reduction. The hypothesis of inadequate responsiveness to environmental factors will be discussed as well.

Biochemical analysis, done after the completion of behavioral experiments, showed significant reduction of noradrenaline content in the brain structures associated with emotional behaviour. We consider the observed changes in serotonin and dopamine levels as an effect secondary to noradrenaline depletion that reflects functional interactions among monoaminergic systems.

111. MECHANISMS OF DRUG AND ALCOHOL ADDICTION (THE ROLE OF LIMBIC SYSTEM, NEUROTRANSMISSION PROCESSES, PSYCHOSOCIAL ASPECTS)

CHARACTERISTICS OF THE SUBSTRATES FOR STIMULATION-INDUCED FEEDING AND REWARD Caterine Bielajew, Monika Trzcinska and Tamara Bushnik School of Psychology, University of Ottawa, 11 Marie Curie, Ottawa, Ontario, Canada, KlN6N5 Current theories regarding the nature of the anatomical circuitry underlying brain-stimulation reward

and stimulation-induced feeding support the view of identical substrates. The conclusion is derived from parametric studies aimed at inferring the electrophysiological properties of the directly stimulated elements underlying.self-stimulation and stimulation-induced feeding. For example, the range of refractory period estimates obtained from sites that give rise to feeding and reward have substantial overlap and a subset of these fibers appears to course along have the same uninterrupted pathway between the lateral hypothalamus and ventral tegmental area, and at similar conduction velocities. Consequently, the resem- blance of their electrophysiological profiles has prompted the idea that the two behaviours share a common substrate, at least in the medial forebrain bundle. In our laboratory, we have extended this functional-anatomical approach to investigate the relationship between self-stimulation and stimulation-induced feeding in cortical structures. Our results indicate that, unlike the medial forebrain bundle, the cortical sites associated with the two behaviours have significantly different anatomical patterns and excitability cycles. A less direct approach has been used to investigate the neurochemical character of the substrates by com- paring their pharmacological profiles, with the focus on compounds that have physiological importance in the modulation of food intake. To date, the evidence from these studies has revealed little distinction, in that treatments that influence reward usually have similar effects on feeding. However, our studies of the peptide, bombesin, a putative satiety agent, have demonstrated a clear dissociation between feeding and reward. The implications of these results towards the identification of the critical neural circuitry are discussed.

1. Trzcidska, M., Bielajew, C.(1992) Behav.Brain Res.48: 1-8 2. Bielajew, C., Bushnik, T.(1994) Pharma.Biochem.Behav.(in press) 3. Bielajew, C., Trzcihska, M.(1994) Behav.Brain Res. (in press)

274 Mechanisms of drug and alcohol addiction

LASTING EFFECTS OF PRENATAL EXPOSURE TO BENZODIAZEPINE AGONISTS AND ANTAGONISTS ON EMOTIONAL BEHAVIOUR AND NEURAL DEVELOPMENT IN THE MOUSE Paul F. Brain, Helena Kurishingal and Colin J. Restall School of Biological Sciences, University College of Swansea, Singleton Park, Swansea, SA2 8PP, Wales, UK There has been a growing appreciation that exposing human foetuses to psychoactive drugs via their

pregnant mothers can have a lasting influence on their behavioural potential in later life. One focus of attention has been the "floppy infant syndrome" involving a high incidence of hypothermia, hyperbilirubi- naemia, hypotonia, asphyxia, respiratory complications and poor suckling responses which has been associated with the mothers ingestion of the benzodiazepine, diazepam. Females are more likely to be clinically treated with this anxiolytic than males so such exposures can be relatively common. Because of the complexities of the situation, attempts have been made to modal the syndrome using laboratory rodents, which facilitates using cross-fostering techniques (to avoid mediated via passage of drug in the milk and/or changed maternal behaviour) as well as raising the possibilities of assessing the effects of drug exposure on a range of biophysical and biochemical phenomena. Pregnant mice were treated subcutaneously each day for last 9- 10 days of pregnancy, with chlordiazepoxide ( Roche Products Ltd., Herts), diazepam (Sigma Chemical Co. Ltd., Poole, Dorset) or the antagonist Flumazepil (Ro 15-1788, Hoffmann-La Roche, Basle, Switzerland) at a range of doses. Their offspring were assessed over development for: - (1) righting reflex (as a measure of neurological development); - (2) cliff avoidance response (as a measure of anxiety); - (3) ultrasonic distress calling ( as a second very reliable measure of anxiety); - v) the changes in membrane fluidities of synaptosomal preparations (as an indicator of the impact of the drug on neurophysiology); - vi) brain contents of cholesterol, phospholipids and protein (as general indicators of neural maturation and factors likely to account for v). The drugs (both agonists and antagonists) had powerful effects on many of these measures, long after their metabolites might reasonably have been expected to have been removed from the neonate's system. Of particular interest are the facts that CDP, diazepam and Flumazepil all retard the righting reflex. CDP and diazepam decreases ultrasonic calling whereas Flumazepil increases it. Flu- mazepil actually has more powerful fluidising effects on membrane systems than do the two agonists. CDP, diazepam and Flumazepil increase the amount of cholesterol in the brain in early postnatal life. Flu- mazepil also decreases phospholipids in both brain and synaptosomal samples. The data is discussed in terms of how prenatal exposure to benzodiazepine-related drugs influence development in neonates and hence mood and adult behaviour in these subjects.

WHY DO 5HT2 ANTAGONISTS NOT REDUCE ALCOHOL INTAKE IN SARDINIAN ALCOHOL PREFERRING (sP) RATS GENETICALLY SELECTED FOR HIGH ETHANOL INTAKE? M. Massi, R. Ciccocioppo, P. Pompei and I. panockal Institute of Pharmacology, University of Camerino, 62032 Camerino, Italy; '~e~artrnent of Behavioral Physiology, Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Jastrzqbiec, 05-551 Mrokbw, Poland The reasons for the failure of 5HT2 antagonists to reduce ethanol preference in sP rats genetically se-

lected for high ethanol preference will be discussed. (I) It has been shown that in sP rats, 5HT2 receptor blockade both with ritanserin and low (1 and 0.1 mglkg) risperidone doses (that produce a marked 5HT2 but low D2 receptor blockade) did not modify 8% ethanol preference. On the other hand, the same drugs markedly reduce ethanol intake in genetically heterogenous Wistar rats (nsW). (2) This sharp contrast be-


tween sP and nsW rats raises the question of whether genetic selection might have resulted in an altered regulation of 5HTergic mechanism in sP animals. (3) To evaluate this possibility, the 5HT2-mediated behaviors wet dog shakes (WDS) and head shakes (HS) were investigated in: (a) sP rats; both naive rats that had never drunk ethanol before the experiments (NasP), and in animals already exposed to 8% ethanol solution (sP); (b) rats from the Sardinian alcohol non-preferring (sNP) line and (c) in nsW rats. (4) WDS and HS induced in NasP and sP rats by senktide (a selective NK3 tachykinin receptor agonist known to stimulate 5HT release in the CNS) as well as by the 5HT agonists, DO1 and quipazine or 5HTP (that en- hances 5HT level in the CNS) were much less intensive than in sNP and nsW rats (in which the intensity of both these 5HT2-mediated behaviors was similar). Thus, it seems that in sP rats selection for high ethanol preference resulted in an inherent suppression of 5HT2 mechanisms. These findings strongly suggest that failure of 5HT2 antagonists to reduce alcohol intake in sP rats is likely due to lower regulation of 5HT2 mechanisms in this animal strain. Moreover, our findings should stimulate investigation as to whether al- teration of 5HT2 mechanisms in animals genetically selected for high ethanol preference might be just an epiphenomenon rather than a neurochemical trait predisposing to high ethanol preference.

BEHAVIOURAL AND PHARMACOLOGICAL HETEROGENEITY IN ALCOHOL-PREFERRING RATS David H. Overstreet Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC, USA The alcohol-preferring P and AA rats were selectively bread for their high voluntary intakes of alcohol.

The Fawn-Hooded (FH) rats, with a genetic serotonin deficiency, also voluntarily consume large amounts of alcohol, but have a lower preference for alcohol than the two selected lines. We have compared these strains of rats with several nonpreferring strains on a number of behavioural tasks which might be expected to or have been reported to differentiate one pair of alcohol-preferringlnonpreferring strains. The P and FH rats tended to be more active in the open field than the AA rats. The P rats were less immobile in the forced swim test than the FH and AA rats, but there were no strain differences at all in the elevated plus maze. All of the alcohol-preferring strains drank substantially more saccharin (0.1 %) solution and alcohol (lo%, V/V) than the nonpreferring strains, but the intake of saccharin was much higher for the P and FH rats, which have been reported to have a serotonergic deficiency, than the AA rats, which have normal or elevated levels of serotonin. The alcohol intake of the AA rats was virtually unaffected by the serotonin releaser, fenfluramine, and the serotonin- 1A agonist, 8-OH-DPAT, but that of the FH rats was dramatically decreased. A number of other drugs known to reduce alcohol intake in rats (TA-0910, bromocriptine, nal- trexone) appeared to have a smaller effect in the AA rats than in the FH rats. These findings indicate that there is both behavioural and pharmacological heterogeneity among the different alcohol-preferring strains.

MECHANISM OF ETHANOL INTAKE INHIBITION PRODUCED BY THE 5HT2 RECEPTOR ANTAGONIST RITANSERIN IN RATS NON GENETICALLY SELECTED FOR HIGH ETHANOL PREFERENCE I. panockal, R. Ciccocioppo and M. Massi '~e~artrnent of Behavioral Physiology, Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Jastrzgbiec, 05-551 Mrokbw, Poland; Institute of Pharmacology, University of Camerino, 62032 Camerino, Italy The suppression of ethanol intake produced in Wistar rats with developed preference for 3% ethanol

by the 5HT2 receptor antagonist ritanserin, as well as the possible mechanism of its action will be dis-

276 Mechanisms of drug and alcohol addiction

cussed. (1) It has been shown that peripheral treatment with ritanserin produces a dose-dependent and long- lasting reduction of the preference for 3% ethanol in normal Wistar rats. (2) Neither this intake (3% ethanol solution + water) nor food intake are affected during drug treatment. (3) The results of intracranial ritanserin injections suggest that the nucleus accumbens is a central site of its action. (4) To clarify the mechanism of drug action, the following possibilities were investigated: (a) 5HT2 receptor blockade has been shown to inhibit tyrosine hydroxylase activity and therefore DA synthesis. This DA deficit can be over- come by treatment with L-dopa (which enters DA synthetic pathway beyond the point of its regulation by tyrosine hydroxylase). L-DOPA administration, however, did not influence the inhibition of ethanol preference produced by ritanserin. Thus, it seems that the ritanserin action does not consist of decreased DA synthesis. (b) Ritanserin increases activity of the mesolimbic DA system. This effect seems to be 5HT- mediated, since serotonin depletion by PCPA prevents it. In our conditions both PCPA and 5,7-DHT abolished ritanserin-induced alcohol preference suppression thus providing evidence that for this effect normal activity of 5HTergic neurons is required. The reduction of the ritanserin effect by the 5HT3 antagonist MDL 72222 that was the most pronounced after its intraaccumbens administration suggests the involvement of 5HT3 receptor in ethanol preference inhibition produced by the drug. Our findings are in keeping with the idea that ritanserin might affect ethanol intake by evoking 5HT-mediated DA release that can substitute for a DA-enhancing ethanol action, making drinking redundant.

PHARMACOLOGICAL PERSPECTIVE ON CALCIUM CHANNEL BLOCKERS FOR ALCOHOL AND DRUG ADDICTION Olgierd PuciIowski Department of Psychiatry and Skipper Bowles Center for Alcohol Studies, University of North Carolina School of Chapel Hill, NC 27599-7175, USA Drugs that inhibit calcium (ca2+) influx through the voltage-dependent L-type channels interfere with

the effects of alcohol and other drugs of abuse that are considered conducive to their addictive potential. ca2+ channel blockers effectively suppress alcohol drinking' and preference in genetic rat models of al- coholism. Comparison of the effects of several compounds from the three main classes of ca2+ channel blockers (dihydropyridines, phenylalkylamines, benzothiazepines) on a free-choice alcohol drinking in rats selectively bred for high alcohol intake will be presented. The issue of tolerance development to this inhibitory effect of ca2+ channel blockers will be explored. ca2+ channel blocker-induced suppression of drinking does not appear to be restricted to alcohol, but rather seems to reflect a more general ability to attenuate hedonic qualities of highly preferred fluids (carbohydrates,saccharin). This raises a question of whether or not these drugs interference with caloric satiety and with gustatory cues of alcohol. ca2+ channel blockers are also known to inhibit rewarding properties of psychomotor stimulants and morphine in tests that do not involve gustatory cues. The ability of ca2+ channel blockers to suppress psychomotor stimulant-derived reward in the conditioned place preference and intravenous self-administration paradigms suggests that their efficacy may involve direct interaction with the central mechanisms of drug reinforcement. ~ d d i t i o n a l l ~ , ~ a ~ + channel blockers have been shown to decrease the intensity of withdrawal symptoms after chronic CNS depressants like alcohol, opiates, benzodiazepines and, to a lesser extent, barbiturates thus interfering with drug-derived negative reinforcement. This multifactorial mechanism of interaction of ca2+ channel blockers with the addictive properties of drugs, together with the behavioral safety of ca2+ channel blockers, should make them feasible candidates for clinical trials in the treatment of alcohol and drug-related problems including craving and relapse.


SELECTIVE BREEDING OF MICE FOR HIGH AND LOW STRESS-INDUCED ANALGESIA: DIFFERENTIATION OF OPIOID-MEDIATED PHENOMENA Bogdan Sadowski Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Jastrzqbiec, 05-551 Mrok6w Poland Exposure to environmental stressors produces a decrease in pain sensitivity in laboratory animals and

humans. This phenomenon, termed stress-induced analgesia (SIA), varies in amplitude among individuals of outbred populations. Depending on reversibility by opioid receptor antagonists such as naloxone or nal- trexone, two forms of SIA are commonly distinguished: an opioid mediated and a nonopioid variety. Either form can be elicited using varying parameters of the same stressor, such as physical intensity, duration or temporal pattern. The magnitude and neurochemical nature of SIA is also known to differ between inbred or outbred strains or laboratory mice and rats. Ten years ago we started to selectively breed an outbred stock of Swiss-Webster mice for high and low magnitude of analgesia caused by a 3 min swim in 20C water, and have developed a high analgesia (HA) and a low analgesia (LA) line. These lines differ not only in the magnitude of analgesia (the trait on which the selection strategy was focused), but also in their neurochemical character (mixed opioidlnon-opioid in HA, and prevailing non-opioid in LA mice). A still more interesting property of the selected lines is their different sensitivity to opiate analgesics. HA mice display lower ED50 values than LA mice for morphine analgesia in the hot plate, tail-flick and for- malin tests which slows that the differences concern both phasic and tonic pain. The two lines also differ in sensitivity to analgesic effects of systemically administered U-50488, a kappa receptor agonist. DAMGO, a specific mu receptor antagonist, and U-50488 are more potent in producing analgesia after intracerebroventricular injection in HA3 than in LA mice. Since HA mice were found to display higher 3 [ HI-naloxone binding in brain tissue, it is assumed that the selection has caused a differentiation of opiate

receptor density in the two lines. The results show that the selection for one particular behavioural trait, such as the magnitude of stress analgesia, has modified the activity of neurochemical systems of the brain controlling intrinsic pain inhibition. This differentiation concerns the mu and kappa subpopulations of central opiate receptors. A common genetic control of the magnitude of stress analgesia and the intrinsic opioid systems activity is suggested. I

Supported by the Polish Committee for the Advancement of Research (KBN), grant No. 50082 91 01.

ORGANIZATION OF THE CENTRAL SYSTEM OF FOOD REWARD AND ITS RELEVANCE FOR DRUG TAKING BEHAVIOUR Weronika Trojniar Department of Animal Physiology, University of Gdansk, 24 Ktadki St., 80-822 Gdansk, Poland Electrical stimulation of several brain structures can elicit specific motivational reactions such as food

and water intake, sexual behavior, exploratory activity, etc. At the same time it can reinforce self-stimulation behaviour. The very same structures were also found to play a role in rewarding properties of drug of abuse. They constitute a hypothetical "brain reward system" - an anatomical entity that is supposed to be responsible for generating reward common to natural stimuli, electrical brain stimulation and abused drugs. In recent years evidence has been accumulated, mainly based on pharmacological studies, that the mesolimbic-mesocortical dopaminergic system is the most essential component of "the brain reward system". However, it seems highly unlikely that a complex central process that we call "reward" can be at.- tributed to only one transmitter in one neural pathway. In a series of experiments we studied the organization of the central system responsible for feeding elicited by electrical brain stimulation that was

278 Motivation, emotions and cognition

characterized by a function relating latency to initiate eating to stimulation frequency (curve shift paradigm). This paradigm allows quantitative assessment of motivational/rewarding (rather than homeostatic) aspects of food intake behaviour. The experimental strategy was to make small electrolytic lesions in a chosen brain structure and to study the effects on feeding elicited by stimulation of another structure. It was found that lesions of the lateral hypothalamus (LH) impair feeding elicited from the ipsilateral, but not the contralateral ventral tegmental area (VTA). Similarly lesions of VTA impair feeding elicited from ipsilateral LH. This impairment manifests as an increase in frequency threshold for feeding and a rightward shift of the latency-frequency function. The results indicate that LH and VTA belong to the same functional system in which impulse flow is bidirectional in the same hemisphere. VTA stimulation-induced feeding was also abolished after ipsi- or contralateral lesions of the anterodorsal thalamic nucleus (AD) and after bilateral destruction of the pedunculopontine tegmental nucleus (PPN). It seems, therefore, that feeding motivation is realized through neural circuitry involving not only dopaminergic elements (such as those in VTA and LH) but also structures outside the mesolibic system (AD and PPN). It was also found that unilateral lesions of VTA and PPN facilitate feeding elicited from contralateral VTA. Interhemispheric organization of feeding circuity is thus complex and it may involve both facilitatory and inhibitory elements. As various experimental variables that affect electrically elicited feeding also influence drug taking behaviour in a parallel manner, it seems reasonable to assume that our results may shed light on the organization of the central system associated with drug abuse.

IV. MOTIVATION, EMOTIONS AND COGNITION (NEUROBIOLOGICAL AND PSYCHOLOGICAL STUDIES)

MOTIVATIONAL MECHANISMS UNDERLYING SEXUAL BEHAVIOUR IN RATS J6zef Beck Department of Physiology, Medical Academy of Warsaw, 26/28 Krakowskie Przedmies'cie St., 00-927 Warsaw, Poland The fact that sexual reward can be a result of exteroceptive stimulation as well as the performance of

the hereditary coordination under the influence of sign stimuli coming from the mate seems to be essential for the explanation of various phenomena observed during sexual behaviour in rats. In male rats precopulatory, copulatory and ejaculatory behavioural patterns consist of hereditary coordinations and uncon- ditionedreflexes, while in females the precopulatory behaviour (sex soliciting) is a hereditary coordination and the copulatory pattern ( lordosis) is an unconditioned reflex. It is suggested that the fluctuation of sexual reward rather than some "copulatory clock" is responsible for temporal pattering of copulatory behaviour in male rats. Moreover: (1) the changes in sexual arousal and sexual reward during sexual behaviour in male and female rats and (2) the role of sexual antidrive and frustration in control of sexual behaviour in rats are discussed.

MOTIVATIONAL DEFICIT IN LEARNED HELPLESSNESS: BEHAVIOUR SLOW-DOWN OR DECLINE OF INTRINSIC MOTIVATION? Mirostaw Kofta Department of Psychology, Warsaw University, 517 Stawki St., 00-183 Warsaw, Poland According to the classical theory of learned helplessness (LH) (3), lengthy exposure to uncontrollable

events results in the emergence of a LH syndrome including cognitive, motivational, and affective deficits. The motivational deficit refers to a reduced tendency to respond voluntary ( behavior slow-down). Re-

Motivation, emotions and cognition 279

search on animal helplessness convincingly demonstrates the existence of such a deficit as distinct from a cognitive (associative) deficit. Until recently, however, laboratory studies of human LH failed to reveal a specific motivational component in the performance decrement following uncontrollable preexposure. The author presents and discusses results of new laboratory and field research suggesting that (1) in human subjects, performance impairment after control loss is attributable mainly to cognitive, not motivational sources (1,2,4, 5) and (2) the motivational LH deficit in humans is a compound of (a) a "classical" response-initiation deficit, and (b) an intrinsic motivation deficit manifested in loss of curiosity and interest in cognitive activity. Recent findings (Sosnowski et al., submitted) imply that whereas the response-initiation deficit is relevant for performance of tasks demanding the application of ready-to-use cognitive programs, the intrinsic motivation deficit appears more important for performance of tasks requiring the development of new rules andlor new cognitive programs (e.g., during creative problem solving). Field research in high school (Sedeck and Kofta, unpublished) confirms the existence of an intimate relationship between helplessness in the achievement area and a decline of intrinsic motivation.

1. Kofta M. (1993) Control motivation and social cognition. Springer Verlag, New York, p. 122-154. 2. Kofta M., Sedek G. (1989) J. Exp. Psychol.: General 118: 3-12. 3. Maier S.F., Selingman M. E. P. (1976) J. Exp. Psychol.: General 105: 3-46. 4. Sedek G., Kofta M. (1990) J. Person. Soc. Psychol. 58: 729-743. 5. Sedek G. et al. (1993) J. Person. Soc. Psychol. 65: 1270-1281.

CONTRIBUTIONS OF THE TEMPORAL LOBE STRUCTURES AND THEIR CONNECTIONS TO MEMORY FUNCTIONS AND EMOTIONAL BEHAVIOUR Danuta M. Kowalska. Nencki Institute of Experimental Biology, 3 Pasteur St., 02-093 Warsaw, Poland Clinical evidence and experimental data on nonhuman primates indicate that damage to the temporal

lobe can disrupt normal memory and emotional behaviour. Memory impairment was first linked to medial temporal lobe damage but subsequent studies have provided more specific information about structures within the temporal lobe and their connections with the diencephalon and prefrontal cortex which comprise neural substrates of memory (1,2). Impaired emotional behaviour in monkeys with damage to the temporal lobe was described first by Kliiver and Bucy over 50 years ago, but the anatomy of emotional impairment still remains unresolved. This work is an attempt to review current knowledge about the role of anterior (AMT) and posterior (PMT) parts of the medial temporal lobe structures and connections in memory and emotional behaviour, as well as the dissociation of their influence in different forms of associative memory or recall. It is suggested that AMT might be critical for crossmodal associations, whereas PMT fills the same role for object-place associations, and both parts of medial temporal lobe are essential for intramodal associative memories. Emotional behavior is substantially affected by AMT, but not by PMT lesions. Ad- ditionally, early damage to the temporal lobe and its eventual influence in infantile autism and hyperactivity are discussed.

1. Mishkin M.M, Appenzeller T.A. (1987) Sci. Amer. 256: 2-1 1. 2. Squire L.R. (1987) Memory and brain. Oxford Press, Oxford, p. 202-224.

STIMULUS SEEKING BEHAVIOUR IN RATS - STUDIES ON INDIVIDUAL DIFFERENCES Wojciech Pisula Faculty of Psychology, University of Warsaw, 517 Stawki St., 00-183 Warsaw, Poland The concept of stimulus or sensation seeking behaviour has been developed in individual differences

psychology. This behaviour is usually interpreted as an expression of the temperamental characteristic of

280 Motivation, emotions and cognition

an individual, human or animal. Rats are the most common animals used in the experiments on stimulus seeking behaviour. A biphasic structure of this behaviour has been found. The first phase is called "infor- mative", the second one "regulative". Our studies have shown complicated development of stimulus seeking behaviour in rats. Both genetic and environmental effects on it's development were found. Analyzing the role of environmental stimulation, we have detected the specific influences of social and physical environment for both phases of the behaviour. The relation of stimulus seeking behaviour to other characteristics was also investigated. We have found a curvilinear relationship between stimulus seeking behaviour and offensive aggressiveness. Rats presenting low and high levels of stimulus seeking activity were more aggressive as compared to rats found to be moderate stimulus seekers. This draws our attention to the problem of emotional processes related to stimulus seeking behaviour. Current studies of stimulus seeking behaviour in rats concern basic organization of behaviour (taxonomical analysis), identifying motivational mechanisms underlying this behaviour and it's adaptive value.

THE LEVEL OF MOTIVATION IS IMPORTANT FOR THE EXPRESSION OF HYPERACTIVITY IN AN ANIMAL MODEL OF ATTENTION-DEFICIT HYPERACTIVITY DISORDER Terje Sagvolden Department of Neurophysiology, University of Oslo, Norway The Spontaneously Hypertensive Rat (SHR) is a strain that is a potential animal model of Attention-

Deficit Hyperactivity Disorder (ADHD) a disorder characterized by attention problems and hyperactivity. Although it can be hypoactive initially, SHR develops a pronounced hyperactivity in most behavioural tests and shows attention-like discrimination problems. Altered reinforcement (reward) processes have been suggested as a mechanism for the development of hyperactivity in SHR as well as ADHD. The hyperactivity seems to depend on the level of motivation in these animals. Compared to controls, SHR show reduced behavioural reactivity to methylphenidate (Ritalin) and d-amphetamine. The reduced reactivity to psychomotor stimulants may be associated with altered dopaminergic function.

TONIC HEART RATE AND DEMANDS: TOWARD A MOTIVATIONAL EXPLANATION Tytus Sosnowski University of Warsaw, Department of Psychology, 517 Stawki St., 00-183 Warsaw, Poland Psychophysiological research on heart rate (HR) suggests two main interpretations of this variable. The

effects of manipulations of incentive, reinforcement/response contingency, and uncertainty speak strongly for the motivational interpretation. On the other side, analysis of HR changes under different task situations suggests a cognitive interpretation. It seems that a source of the motivational-cognitive controversy lies, first of all, in the nature of task demands. According to our hypothesis, higher tonic HR increase is expected when a task can be solved by means of ready-to-use programmes (e.g., during performing well learned arithmetic operations) than when such programmes are lacking and have to be formed and tested (e.g., during solving the series test). In a 2 x 2 ~ 2 experiment (n=112), three independent variables were manipu- lated: (1) kind of task (arithmetic vs series test), (2)reward, and (3) experience with uncontrollability. In agreement with the hypotheses, HR increase was much higher during the arithmetic than series test, as well as under the reward than non-reward condition. The results lead to the conclusion that tonic HR is, first of all, an index of incentive motivation and the HR changes observed during problem solving reflect mainly changes in motivational processes.

Posters 281

POSTER SESSION

ROLE OF THE CHOLINERGIC AND GLUTAMINERGIC TRANSMISSION IN THE CONTROL OF ULTRASONIC VOCALIZATION IN THE RAT S.M. Brudzynski and X-W. Fu Department of Clinical Neurological Sciences, University of Western Ontario, London, Ontario N6A 5C1, Canada The emotional-aversive response, induced by intracerebral injections of carbachol, represents a phar-

macological response relevant to some forms of the natural defensive behaviour. The carbachol-induced response can be induced from an elongated medial strip of tissue extending from the septa1 and preoptic- anterior hypothalamic regions caudally along the third ventricle. Intracerebral injections of carbachol or other muscarinic agonists into these regions of the rat brain induces a behavioural response with prominent ultrasonic vocalization. The vocalization has a sound frequency (pitch) between 20 and 32 kHz and is usually referred to as 22 kHz calls and consists of long calls (more than 300 ms), with little or no frequency modulation and narrow bandwidth (below 5 kHz). As demonstrated in our previous studies, carbachol has a predominantly inhibitory effect on spontaneously firing neurones in the hypothalamic-preoptic region. The question arises whether or not excitation of hypothalamic-preoptic neurones by an excitatory amino acid will have behavioural effects with concomitant vocalization. Direct injection of glutamate into the anterior hypothalamic-preoptic region of 25 rats induced changes in behaviour and ultrasonic vocalization. The vocalization, however, was different from 22 kHz calls. Glutamate-induced vocalization was characterized by short duration calls (below 60 ms) of high sound frequency, mostly above 40 kHz and was similar to the known 50 kHz vocalization observed in natural situations. The glutamate-induced vocalization was dose dependent within the dose range of 16.9-67.6 kg and was antagonized by local pretreatment with MK-801, an NMDA antagonist. The increasing dose of glutamate induced more calls and had a significant influence on the frequency and intensity of emitted ultrasound. The average sound frequency increased while the mean duration of a single call and the bandwidth did not significantly change with doses of' glutamate. Injection of carbachol, a muscarinic cholinergic agent, into the same brain sites as glutamate, induced a different type of ultrasonic vocalization with low sound frequency and long call duration, known as 22 kHz calls. The results suggest that high sound frequency, short duration calls (50 kHz) and low sound frequency long duration calls (22 kHz) have different neurophysiological and neurochemical mechanisms. Our findings may also corroborate behavioural observations from other studies that 22 kHz calls, which are associated with aversive and defensive situations, and 50 kHz calls, which are associated with aggressive and other social encounters have different neural and neurochemical mechanisms.

Supported by the NSERC of Canada.

STRUCTURAL-FUNCTIONAL ORGANIZATION OF CONDITIONED REFLEXES AND DELAYED REACTIONS IN CATS Alex Chikadze Memory Research International Centre, I. Beritashvili Institute of Physiology, Georgian Academy of Sciences, 14 Gotua St., Tbilisi 380060, Georgia The peculiarities of structural-functional organization of a conditioned reflex at different stages of its

elaboration and delayed reactions were studied. In one group of cats, conditioned reflexes were elaborated to sound stimuli and delayed reactions were tested by the direct and indirect methods under the conditions of possible self-stimulation of the septum. It was established that at the initial stages of the elaboration of conditioned reflexes and also while testing delayed reactions to sound signals and natural stimuli, the time

282 Posters

of self-stimulation of the septum increased considerably. In a second group of animals, during the whole experiment the electric activity of the association cortex and dorsal hippocampus was recorded by means of a telemetric system. It was established that the stage of the elaboration and the beginning of the union of the conditioned reflexes is characterized by aregular theta-rhythm in the hippocampus and desynchroni- zation of electric activity in the cortex. As the conditioned reflexes strengthen, the regularity of the hippocampal theta-rhythm decreases and alpha-rhythm appears in the electric activity repeatedly, according to the direct and indirect methods. The drop in emotional strain and suppression of hippocampal theta- rhythm are not observed.

THE ROLE OF 5-HT IN FEAR-RELATED BEHAVIOUR OF MALE MICE -and Milos KrSiak Institute of Pharmacology, 3-rd Medical Faculty, Charles University, 87 Ruska St., 100 00 Prague 10 and Institute of Pharmacology, Czech Academy of Sciences, 1083 Videiiskh St., 142 20 Praha 4, Czech Republic 5-HT has been reported to play an important role in regulatory mechanisms of anxiety (4). New ther-

apeutic approaches use ~ - H T ~ A full or partial agonists, 5-HT2 antagonists and 5-HT3 antagonists (1). Sig- nificant differences, however, were found between some clinical studies and animal experiments. 5-HT receptors in the brain are very heterogenous and various types and subtypes may be involved in various specific functions. Traditional approachs of behavioral pharmacologists usually focus on avoidance or preference for open or new environments, time spent in light/dark areas etc. One can speculate that such activities could be considered as anti-predatory behaviours. In contrast, human beings frequently suffer from disturbed social relationships that may lead to distress and anxiety. Thus, using ethological techniques, we have analyzed the effects of 5-HT drugs on spontaneous strategies of social behaviour exhibited by individually-housed male mice in intraspecies conflict situations. Some males readily attacked their opponents, while others displayed fear-related defensive-escape behaviour towards non-aggressive opponents (timid mice). This behaviour has been described as a good marker of anxiolytic activity of drugs (2). Our results showed that the defensive-escape behaviour, as well as other activities, shown by the timid mice remained nearly unaffected by DAU 6215 (with high affinity for 5-HT3 receptors). Similarly, there were no striking effects of the 5-HT2 antagonist ritanserin on fear-related behaviour, but it raised the pre- aggressive activities (threat, tail rattle) in some previously non-aggressive animals. A statistically significant and dose-dependent reduction of defensive-escape behaviour was found in timed males treated with eltoprazine, predominantly acting on 5-HTi receptors. This drug is known for its antiaggressive effects and, indeed, it completely blocked aggressive behaviour in aggressive males. Even though the range of the tested drugs is far from complete, our results suggest that the effects of 5-HT are not selective to fear- related social behaviour. The close relationship between aggressive and defensive-escape behaviours that was also found in our experiments with typical anxiolytic drugs (benzodiazepines), might suggest that separate concepts of aggression and fear are incorrect. The effects of both antiaggressive (i.e.,eltoprazine) and anxiolytic drugs (i.e.,diazepam) on aggressive and defensive components occurring in social conflict may support the reality of a common functional mechanism of competitive behaviour, originally described by Scott and Fredericson (3) as "agonistic behaviour".

1. Gothert M. (1992) Arzneim.-Forsch./Drug Res. 42,12a: 238-246. 2. KrSiak M. et al. (1984) Ethopharmacological aggression research. Inc. Alain R. Liss, New York, p. 93-1 14. 3. Scott J.P., Fredericson E. (1951) Physiol. Zool. 24: 273-309. 4. Stein L. et al. (1973) The Benzodiazepines. Raven Press, New York, p. 299-326. Supported by grant of the Czech Academy of Sciences #70852.

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CHANGES IN THE RESPIRATORY PATTERN AS AN INDICATOR OF FEAR IN RATS Piotr Jelen, Stefan Sdtysik, Jolanta Zagrodzka and Stefan Kasicki Nencki Institute of Experimental Biology, 3 Pasteur St., 02-093 Warsaw, Poland Behavioural research, and especially psychopharmacology, need a reliable, continuous and easily quan-

tified measure of fear. Conditioned respiratory suppression (CRS) originally measured via nasal thermistor and defined as a decrease in respiratory amplitude was reliably observed in cats anticipating an aversive stimulus (1). The most popular animal for investigating the pharmacological properties of anxiolytic drugs is the rat. Therefore, the aim of our study was to verify whether the CRS procedure designed for cats could be used in rats as well. For practical reasons, the thermistor measurement had to be replaced by diaphrag- matic EMG. Electromyographically measured CRS, respiratory rate, tonic EMG level and the mean EMG level were used as measures of the acquired fear. Chronic EMG electrodes were implanted into the rats' diaphragm. Animals were adapted to the spacial apparatus which restricted their movements. Daily training session consisted of ten trials separated by 2-minute breaks. Data from 10 seconds prior to the tone CS served as baseline. A five second tone (500 Hz) was paired with an electric shock (lms, 3mA) to the tail. In all rats the onset of the tone was marked by an increase in the respiratory rate. There was also a reduction of the respiratory amplitude, except for the initial 2-3 deep breaths immediately after the tone onset. The CRS effect, however, was much less pronounced than the CRS described in cats. The results indicate than the CRS procedure might be useful in rats, especially because our preliminary results with Baclofen (anxiolytic-type drug; lOmg/kg) treated rats showed a reduction of a reactivity and a smaller CRS effect after injection. Some rats, however, displayed a different pattern of respiratory reaction i.e., an increase of the respiratory amplitude during the warning stimulus. This effect seems to be associated with the individual emotional characteristics of the animal and its coping strategy. The mean as well as the tonic EMG level increased during the presentation of the tone. Concluding, CRS alone observed in rats in anticipation of noxious stimuli is not a reliable phenomenon across the subjects as it was described in cats. Nevertheless, the EMG analysis of the full pattern is useful as an indicator of conditioned fear.

1. Soltysik S. et al. (1988) Anim. Learn. Behav. 16: 177-184

SLEEP-WAKING PATTERN AND MOTOR ACTIVITY AFTER LATERAL HYPOTHALAMIC DAMAGE Edyta Jurkowlaniec, Jolanta Orzd-Gryglewska and Weronika Trojniar Department of Animal Physiology, University of Gdarisk, 24 Ktadki St , 80-822 Gdahk, Poland Electrolytic or chemical lesions of the lateral hypothalamus (LH) produce severe motivational deficits ac-

companied by signs of general behaviour depression. In our previous experiments we found that bilateral damage to this area increased EEG waking activity and reduced the amount of slow wave sleep and paradoxical sleep (insomnia). We also found that although overt locomotor activity of LH rats is severely depressed they are in fact in a state of continuous motor restlessness. Their activity consists mainly of perioral movements and slight postural adjustments. In these experiments we studied whether there is a causative relationship between LH motor hyperactivity and insomnia. Haloperidol (HP) (5.0 mglkg i.p.) was used to suppress motor activity, and its consequences for EEG sleep-waking pattern were analyzed in male Wistar rats before and after bilateral lesion of the LH. EEG was recorded from cortical and hippocampal electrodes for 1 h daily (morning hours). Motor activity was measured concomitantly with the EEG by means of an electrodynamic activity meter and processed by a computer analyzing system. In LH rats waking time was increased by about 28% in comparison to the prelesion level. Slow wave sleep was reduced by about 22% and paradoxical sleep by about 6%. At the same time, motor activity was more than 3 times higher than before the lesion. HP suppressed lesion-induced motor hyperactivity to a level close to the level of prelesion activity. However, the effect of HP on the sleep-

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walung pattern was not significant, although waking time became slightly reduced after HP injection. The results do not support the hypothesis of causative relations between motor hyperactivity and insomnia after LH lesion and suggest that both phenomena depend on destruction of separate functional systems.

AGGRESSION AND FRONTAL LOBE DEFICITS Bozydar L.J. Kaczmarek Institute of Psychology, UMCS Lublin, 5 Plac Litewski, Poland Patients with frontal syndrome show considerable deviations of their language output. Therefore, they

were asked to (1) repeat a story, (2) describe pictures, and (3) talk about a given topic to facilitate their language production. Two experimental groups were selected: 8 schizophrenic subjects who committed serious crimes (Group A), and 8 aggressive patients with frontal lobe lesions (Group B). Four control groups without any history of violence included: 8 schizophrenic subjects (Group C), 8 frontal subjects (Group D), 8 posterior brain-damaged patients without aphasia (Group E), and 8 non brain-damaged subjects (group F). A careful analysis of the structure of narratives elicited form the subjects revealed significant similarities between group A and B. They both exhibited distinct features which were also reflected in the gross deformation and simplification of the structure of their narratives. The score of the other groups differed to a significant degree from the above "aggressive" groups. Another distinctive feature of the delinquent groups was their blunt affect which reflects a lack of concern for the events of the surrounding world. It is connected with the fact that the frontal lobes not only play an inhibitory role in behaviour but also give an emotional colour to our experience.

INTERACTIONS BETWEEN SACCHARIN AND ALCOHOL Alexey Kampov-Polevoy, D.H. Overstreet, O.P. Kashevskaya, I.V. Viglinskaya, B.A. Badistov, S.B. Seredenin and J.A. Halikas Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC, 27599-7175, USA Previous reports established that there was a high positive association between saccharin and alcohol

intakes in rats and mice (1,2). The present two studies further examined the relationship between saccharin and alcohol intakes. In the first study, the association was examined in 8 strains of alcohol preferring (P, AA, Fawn-Hooded) or nonpreferring (NP, ANA, Flinders Resistant Line, Madusleys) rats. There was a significant positive association between saccharin and alcohol intake but it was not as high as has been reported previously. This lower correlation was mainly the result of the alcohol-preferring AA rats drinking less saccharin than the P and Fawn-Hooded rats and the alcohol-nonprefening Maudsley rats drinking more saccharin than expected. In the second study, the consequences of prior access to saccharin was examined because the alcohol intakes in the association studies were lower than typically reported for the alcohol-preferring strains. Access to saccharin (0.1 %) in a free choice with water in P and Fawn-Hooded rats results in substantial intakes of saccharin (>250 mVkg per day) over four days and led to areduction of alcohol intake of approximately 30%, which lasted for one week. The possible involvement of opiate mechanisms in these phenomena will be discussed.

1. Belknap J. et al. (1993) Psychopharmacology 112: 503-5 10. 2. Overstreet D. et al. (1993) Alcohol. Clin. Exp. Res. 17: 366-367.

FACILITATION OF VTA STIMULATION-INDUCED LOCOMOTOR ACTIVITY AFTER CONTRALATERAL VTA LESION Ilona Klejbor and Weronika Trojniar Department of Animal Physiology, University of Gdahk, 24 Madki St , 800-822 Gdahk, Poland Forward locomotion is a very commonly observed response to electrical or chemical stimulation of the ven-

tral tegmental area (VTA) and the lateral hypothalamus. From the very same locations feeding reactions and

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self-stimulation can be obtained. In our previous work we found that unilateral lesions of VTA cause facilitation of feeding elicited by electrical stimulation of the contralateral VTA and we postulated that such contralateral facilitation may constitute an important mechanism of brain plasticity. In the present experiment we studied whether "contralateral facilitation" would also hold for other electrically elicited behaviors such as forward locomotion. In male Wistar rats latency to initiate locomotion was measured as a function of VTA stimulation frequency. Then, unilateral lesions of the contralateral VTA were performed and latency-frequency functions were determined daily for 5- 14 days postlesion. It was found that unilateral electrocoagulation of VTA facilitated locomotion activity elicited from VTA electrodes located in the other hemisphere. This facilitation manifested as a decrease in frequency threshold (up to 43% of the prelesion baseline) and leftward shift of the latency-frequency function. On the other hand, lesions localized outside VTA (lateral hypothalamus, thalamus) impaired locomotor reactions. The results provide further evidence that anatomically specific facilitation of function of the intact hemisphere may be a common compensatory response to unilateral brain injury.

EMOTIONAL STATE AND AMYGDALA-ACCUMBENS INFORMATION FLOW IN FREELY MOVING RATS Anna Korzeniewska, Stefan Kasicki and Jolanta Zagrodzka Nencki Institute of Experimental Biology, 3 Pasteur St., Warsaw 02-093, Poland Nucleus accumbens (ACC) is considered to be a modal point between the motivational and executory

systems in the brain. The purpose of our experiment was to determine the functional character of the limbic-motor connections, studying the information flow among nervous structures by means of a multifactor EEG analysis. The limbic system is connected with the basic motor structure via the projection from the basolateral amygdala (BLA) and ventral subiculum (SUB) to the nucleus accumbens. Thus, we decided to analyze the interaction among these structures during various emotional states in freely moving rats. EEG electrodes were implanted into the ACC, BLA and SUB. Rats were tested in nonstressful locomotion tasks and simultaneously the EEG activity was recorded. Afterwards, the EEG signals were analyzed with the use of a new method (1) enabling analysis of the directions, intensities and frequency bands of the information flow between the structures mentioned above. This analysis is based on the calculation of the directed transfer function (DTF), and partial, ordinary and multiple coherence. It was found that, in general, the strongest interactions were between ACC and BLA. The direction of dominant influence, however, altered depending on the emotional state of the animal. In non-stressful, well known situations the information flow from ACC to BLA was dominating. In stressful tasks, on the contrary, the influence of BLA on ACC increased. This suggests that this direction became dominating. The small activity flow from ACC to SUB, and from SUB to BLA did not depend on the rat's behaviour. We conclude that the emotional-motivational state of the animal affects all the parameters describing the information flow (direction, intensity and frequency band) between the nucleus accumbens and amygdala, and indicates the functional interactions of the limbic and motor systems.

1. Kamifiski M., Blinowska K. (1991) Biol. Cyber. 65: 203-210. Supported by the Committee for Scientific Research (KBN), grant No. 66371.

STUDIES ON THE EFFECTS OF 5-HT-3 RECEPTOR ANTAGONISTS IN AN ANIMAL MODEL OF ETHANOL DEPENDENCE Wojciech Kostowski, Wanda Dyr and Ewa Jankowska Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, 119 Sobieski St., 02-597 Warsaw, Poland The possible involvement of serotonergic 5-HT-3 receptors in the central effects of ethanol (ET-OH)

has been the subject of several studies. We studied the effect of two 5-HT-3 antagonists, tropisetron and

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ondansetron, on withdrawal and ET-OH preference in Wistar male rats. Low doses of drugs (0.00025- 0.001 mgkg i.p.) reduced ET-OH intake in high preferring animals. The effect of tropisetron was unchanged in 5-HT depleted rats (by means of 5,7-DHT icv injection), but was attenuated in rats treated with 6-hydroxydopamine. Both ondansetron and tropiosetron reduced ET-OH intake after microinjection into the limbic areas (amygdala and nucleus accumbens). ET-OH withdrawal audiogenic seizures were reduced in rats treated with 5-HT-3 antagonists. The data may provide an indication of 5-HT-3 antagonist's possible site of action in ET-OH dependence.

INHIBITORY INFLUENCE OF 6-HYDROXYDOPAMINE ADMINISTRATION INTO THE HYPOTHALAMIC PARAVENTRICULAR NUCLEUS ON CARBOHYDRATE INTAKE IN CATS Maria Krotewicz Department of Neurophysiology, The University of L6di, 66 Rewolucji 1905 . St., 90-222 L6di, Poland Numerous studies have demonstrated that the noradrenergic system in the hypothalamic paraventricu-

lar nucleus (PVN) is involved in the control of feeding behaviour and appetite regulation. Noradrenaline (NA) injections into this nucleus elicited feeding responses in satiated rats. This hypothesis was supported by experiments in which 6-hydroxydopamine (6-OHDA) administration into the PVN that revealed a deficit in daily food intake, particularly of carbohydrate consumption. In the present study we have investigated the effects of 6-OHDA administered into the PVN on food intake in cats. During a 1-hour test we have measured the following parameters: food intake, duration of eating and eating frequency (i.e., number of eating bouts) of three kinds of food (i.e., cereal, raw horse meat and milk). It was found that the administration of 6-OHDA significantly decreased cereal and milk intake while the consumption of meat was not changed. Moreover, 6-OHDA administered into the PVN exerted suppressing effects on eating frequency and duration of cereal intake with no effects on milk or meat consumption. These results indicate that the 6-OHDA administration into the PVN in cats reveals inhibitory effects on ingestion of foods rich in carbohydrates, as has been previously shown in rats. This leads to the conclusion that the PVN mechanisms regulating carbohydrate ingestion may possess an interspecies character.

GVS-111, A NOVEL COGNITIVE ENHANCER WITH ANXIOLYTIC PROPERTIES Rita Ostrovskaya, T.A. Gudasheva, T.A. Voronina, T. Garibova, H. Valdman, D.H. Overstreet, S. Seredenin and J. Halikas Institute for Pharmacology, 8 Baltiyskaya St., 12315 Moscow, Russia The present studies report on the effects of GVS- 11, a novel substituted dipeptide, on counteracting

memory impairment induced by various treatments and withdrawal anxiogenesis following chronic diazepam treatment. In the dose range of 0.1-1.0 mgkg, GVS-111 significantly counteracted the memory impairment induced by electroconvulsive shock, acutely administered scopolamine (0.8-1.0 mgkg), or chronically administered scopolamine (1.0 mgkg daily for three weeks, followed by 10 days washout). In a comparative study a dose of 200 mgkg piracetam was required to achieve the same degree of memory improvement. In another series of studies, rats were injected daily with diazepam (4 mgkg) for three weeks and acutely withdrawn. Diazepam-withdrawn rats spent much less time in the open arms of an elevated plus maze than vehicle-treated rats. Diazepam-withdrawn rats treated with GVS (0.5 mgkg) spent as much time in the open arms as the vehicle-treated rats. Diazepam-withdrawn rats treated subchronically with GVS (0.5 mgkg daily for 7 days) actually spent more time in the open arms than any other group. These findings indicate that GVS-111 has both cognitive-enhancing and anxiolytic properties.

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THE EFFECT OF SEROTONIN DEPLETION AND INTRA- HIPPOCAMPAL MIDAZOLAM ON RAT BEHAVIOUR IN THE VOGEL CONFLICT TEST M. Nazar, R. Stefanski, A. Bidzinski, M. Jessa and A. Ptainik Department of Pharmacology and Physiology of the Nervous System Department of Biochemistry, Institute of Psychiatry and Neurology, 119 Sobieski St., 02-957 Warsaw, Poland The aim of this study was to examine the question of a structural link between limbic serotonin mech-

anisms and anticonflict action of benzodiazepines. In the experiment, p-chlorphenylalanine (a serotonin synthesis inhibitor, p-CPA) was used to obtain depletion of serotonin (5-HT) and 5-hydroxyindoloacetic acid (5-HIAA) in the hippocampus. The anxiolytic effect of short acting imidazobenzodiazepine (rnida- zolam) microinjected into dentate gyms of the hippocampus was examined in animals with inhibited serotonin transmission . A modified Vogel test was used to evaluate midazolam and p-CPA anticonflict influence. As a control for the Vogel test, open field motor activity, spontaneous water intake and shock threshold level were measured in 5-HT depleted and midazolam injected animals. p-CPA administered three days before testing significantly increased punished water intake in the Vogel test. Motor activity and spontaneous water intake in control experiments remained unchanged. Shock threshold level in the p-CPA treated group was slightly lowered. Midazolam administrated to the dorsal hippocampus at a dose of 10gIsite also disinhibited punished behavior in the Vogel test. Administration of midazolam did not change any of the controlled parameters except for open field motor activity which at this dose was decreased. Midazolam retained its effect when given to rats withp-CPA-induced 5-HT depletion. Moreover, this effect was significantly stronger than in thep-CPA alone pretreated group. Results of this experiment suggest that the anticonflict effect of serotonin depletion and hippocampally administered benzodiazepine may occur independently. The data also confirm specific involvement of serotonin in emotional behaviour and point at the hippocampus as the key structure in processing of emotional input.

BEHAVIOURAL MODULATION OF EXCITABILITY OF a-MOTONEURONS OF THE SOLEUS MUSCLE IN RATS Beata Sokdowska and Julita Czarkowska-Bauch Department of Neurophysiology, Nencki Institute of Experimental Biology, 3 Pasteur St., 02-093 Warsaw, Poland Modulation of excitability of a-motoneurons in various behavioural states was studied in awake rats

by means of the Hoffmann (H) reflex, an analog of the monosynaptic stretch reflex in the soleus muscle. H-reflex amplitude depends on the net effects exerted by segmental and supraspinal influences on a-mo- torneurons. Thus, it was analyzed as a function of: (1) Ia stimulus strength, (2) the amplitude of muscle activity before stimulus application (background EMG), (3) the amplitude of direct motor (M) response and (4) behaviour of the rat. Our aim was to estimate the H-reflex amplitude modulation under various emotional states of the animal. The H-reflex was elicited by direct electrical stimulation of the Ia fibers of the tibia1 nerve with chronically implanted bipolar cuff electrode and recorded with a bipolar electrode implanted into the soleus muscle. The emotional state of the animal was estimated by means of the background EMG activity of the soleus muscle and the animal's behaviour. The smallest variability of the background EMG was observed while the rats were quietly sitting and eating. Under these conditions, the amplitude of the test H-reflex (at a stimulus strength near the threshold of M response) was over two times higher (from 2.1 to 2.6) than the background EMG. It corresponded to 21%-56% of the maximal amplitude of H-reflex. In contrast, in somnolent rats, the background EMG activity dropped to zero and the probability of eliciting H-reflex was drastically reduced. In emotionally excited rats climbing up a wall of the cage, the background EMG activity was so high that its ratio to the amplitude of H-reflex was below 50%. Our observations indicate that a prerequisite for measuring modulation

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of a-motoneurons in various emotional states by means of the H-reflex is a moderate level of background EMG. It was found that at moderate background EMG, a digging and self-grooming behaviour (which in rats might express anxiety and quietness, respectively) highly modulate excitability of a-motoneurons of the soleus muscle.

Supported by the State Committee for Scientific Research, grant No. 663179203.

THE EFFECT OF GROUP SIZE ON RESPONSE TO ANIMAL PREY IN WORKERS OF THE WOOD ANT FORMICA POLYCTENA FORST KEPT IN QUEENLESS AND BROODLESS GROUPS Anna Szczuka and Ewa J. Godziriska Department of Neurophysiology, Nencki Institute of Experimental Biology, 3 Pasteur St., 02-093 Warsaw, Poland Much previous literature show that the size of an ant colony may have a profound effect on foraging

and predatory behaviour in the ants. In many ant species workers of small, immature colonies do not hunt. As their colony grows, the ants first start to show scavenging behaviour (retrieval of dead animal prey), and later they start to hunt. Hunting tactics and recruitment strategies of the ants are also know to depend on the colony size. On the other hand, it is generally assumed that scavenging and hunting behaviour is a fairly direct response of the ants to the presence of larvae. Our present data demonstrate that workers of the wood ant Formica polyctena Forst may continue to retrieve insect prey to the nest for many months even if they are kept in queenless and broodless group. However, such behaviour is retained only if the size of the group is sufficiently large (over 35-45 individuals). In groups counting less than 35 individuals, the workers retrieve the prey to the nest only rarely, although they may continue to bite the prey andlor to carry it. In very small groups (less than 20 individuals), the responses of workers to dead insect prey are usually limited to antenna1 contacts, although the general activity of the ants continues to be normal. The effect of group size on responses of workers of F. polyctena to animal prey is fairly flexible. When large groups were subdivided into smaller ones, below the "threshold size" of about 35 individuals, the tendency to retrieve the prey to the nest gradually disappeared. The larger the initial group before its subdivision into smaller ones, the slower was the extinction of the tendency to retrieve the prey. The time during which the scavenging behaviour was retained in these small groups showed a highly significant positive correlation with the initial group size. When small groups in which the retrieval of animal prey was no longer observed were combined again into larger ones, the tendency to retrieve prey reappeared very quickly by the next day. When we gradually add individuals to small groups in which the retrieval of animal prey was not observed, the tendency to retrieve prey reappeared when the group attained the "threshold size" of about 35-45 individuals. Our preliminary observations also suggest that the effect of group size on responses of the ants to animal prey appears only if the individuals can have close physical contacts. Olfactory stimuli alone do not seem to be sufficient to produce this effect. Our present data thus demonstrate that workers of F. polyctena may continue to retrieve animal prey to their nests for many months even in the absence of a queen and of brood if they are living in sufficiently large groups. We can thus conclude that the expression of scavenging behaviour depends mainly on the group size and does not depend directly on the presentlabsence of the queen and the larvae. Our data also show that theeffects of group size on response of F. polyctena to insect prey are flexibile and reversible.

INVOLVEMENT OF THE ANTERODORSAL THALAMIC NUCLEI IN FEEDING INDUCED BY STIMULATION OF THE VENTRAL TEGMENTAL AREA Matgorzata Staszewska and Weronika Trojniar Department of Animal Physiology, University of Gdahk, 24 Kladki St , 80-822 Gdansk, Poland Feeding behaviour can be induced in satiated animals by electrical stimulation of several brain loci,

especially those lying in the lateral hypothalamus and the ventral tegmental area (VTA). However, the

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organization of neuronal circuity subserving feeding is not well understood. In the present experiment we studied possible involvement of the anterodorsal thalamic region in eating elicited by stimulation of VTA - a key structure of the mesolimbic-mesocortical system. In rats which fed in response to electrical VTA stimulation, latency to initiate feeding was measured as a fGnction frequency. Then, unilateral, electrolytic lesions were made in the anterodorsal thalamic region, and latency-frequency functions were determined daily for 7-14 days postlesion. It was found that unilateral electrocoagulation of the anterodorsal thalamic nucleus (AD) impaired feeding elicited by stimulation of VTA, ipsi- or contralaterally to the lesion. This impairment manifested as an increase in frequency threshold for feeding and a rightward shift of the function relating latency to initiate feeding stimulation frequency. Threshold elevation ranged from 13.6% (ip- silaterally) to 25.2% (contralaterally) of the prelesion value. No major effect on feeding was found after lesion of the thalamic tissue neighboring AD. These results suggest the existence of bilateral comrnuni- cation between VTA and AD in the control of feeding behaviour.

NEUROCHEMICAL BASIS OF THE FEAR REACTION Magdalena Strzelczuk and Andrzej Romaniuk Department of Neurophysiology, University of L6di, 66 Rewolucji 1905r. St., 90-222 L6di, Poland The influence of intrahypothalamic injections of the N-cholinergic receptor antagonists D-tubocurarine

(DT) or a- bungarotoxin (BTX) and of GABAA-ergic receptor antagonist bicuculline (BM) and an agonist of this receptor, muscimol (MSC), on fear response (FR), motility (M) and monoaminergic systems activity in emotional brain regions (hypothalamus, midbrain, amygdala) and frontal cortex in the cat was investigated. Injections of DT and BM produced similar behavioural changes typical for the FR, i.e., an increase of characteristic vocalization time and an increase of M and neurochemical changes, i.e., an increase in noradrenaline level in all investigated brain areas and an increase of DA system activity in the amygdala. BTX did not produce any behavioural or biochemical changes. MCS did not produce any behavioural changes but did produce decrease in DA system activity in the hypothalamus, midbrain and frontal cortex. This observation had led us to the following conclusion: the triggering mechanism of the FR depends on the blockade of N-cholinergic and GABAA-ergic receptors.

IN SEARCH OF THE FOREBRAIN REWARD SUBSTRATE: A CAUDATE-PUTAMEN AND MEDIAL PREFRONTAL CORTEX MAPPING STUDY Monika Trzcinska and Catherine Bielajew School of Psychology, University of Octtawa, 11 Marie Curie, Ottawa, Ontario, KlN6n5, Canada There is a growing consensus that forebrain structures, such as the caudate-putamen (CPu) and the me-

dial prefrontal cortex (MPFC) constitute a separate reward system from that of the medial forebrain bundle. Behavioural and electrophysiological studies have shown that acquisition of forebrain self-stimulation is more gradual than that of the medial forebrain bundle and the behaviourally derived refractory periods tend to be longer than the ones reported for midbrain sites. In addition, studies aimed at evaluating the functional connectivity between these two regions indicate some integration of the MPFC and CPu reward signals and little or no summation of the rewarding effects derived from combined MPFC and the medial forebrain bundle stimulation. In view of these results, the aim of the present study was to systematically document the distribution and current-frequency relationship of MPFC and CPu sites that support self- stimulation. Male Hooded rats were implanted with two moveable electrodes aimed at the CPu and MPFC. Frequency thresholds were determined at each site by evaluating the rate of bar pressing at a range of fre-

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quencies, from values that produced no responding to ones that gave rise to maximal rates; the threshold, which corresponded to 50% of the maximal rate, was obtained by interpolation of the rate-frequency function. Thresholds were determined at each of three currents in order to generate current-frequency trade-off functions; the currents of the cathodal 0.1 msec squere-wave pulses ranged from 200 to 1000 fA. Of the 350 sites that were valuation 6% supported MPFC self-stimulation and 13% in the case of the CPu sites. Both areas exhibited similar frequency threshold ranges, roughly between 8 and 42 Hz. Historical analysis revealed a cluster of positive sites in the Cgl, Cg3, Frl, and Fr2 portions of the MPFC and in the ventromedial regions of the CPu. The spatial properties of the substrates, inferred from the trade-off data, are discussed.

1. Trzciriska M., Bielajew C. (1992) Behav. Brain Res. 48: 1-8 2. Trzciriska M., Bielajew C. (1993) Soc. Neurosci. Abstr. 19: 809.

STIMULUS MODALITY EFFECTS ON FORWARD AND ON BACKWARD CER CONDITIONING IN RATS Grazyna Walasek, Malgorzata Wqsierska and Kazimierz Zielinski

Department of Neurophysiology, Nencki Institute of Experimental Biology, 3 Pasteur St., 02-093 Warsaw, Poland Presentation of novel stimuli resulted in a decrease in the rate of bar pressing. As shown in the recent

experiment (1) this attenuating effect was the strongest during first onset of the stimulus. The effect ha- bituated more rapidly for a noise than for a darkness stimulus. After habituation later onsets of the noise elicited an enhancement and terminations of the noise resulted in a decrease of the response rate. The darkness generated opposite effects in response rate but only after longer habituation. The opposite effects of the same stimuli were more evident for stimuli of shorter than of longer duration.

In the present experiment the effectiveness of the same stimuli was examined in forward and in backward CER conditioning paradigms in male hooded rats. It was revealed that during training both stimuli were equally effective in forward conditioning, probably due to the floor effect of the suppression. How- ever, the suppressive effect of darkness was more resistant to extinction. On the contrary, in backward conditioning the bar press rate was higher to the noise than to the darkness.

1. Walasek G. et al. (1994) Acta Neurobiol. Exp.54: 133-141.

POST-STRESS ANALGESIC REACTIVITY IN RATS WITH PARTIAL AMYGDALA LESION Tomasz Werka Department of Neurophysiology, Nencki Institute of Experimental Biology, 3 Pasteur St., 02-093 Warsaw, Poland The role of the dorsal basal and the central nuclei of the amygdala under two modes of foot-shock an-

algesia was studied in 45 male Moll-Wistar rats. In Experiment I a stressor was a 4 min continuous foot- shock, eliciting analgesia dependent on neural mechanism. In Experiment I1 analgesia was produced by regular intermittent 20 min of foot-shock which was evoked by an opioid, humorally mediated mechanism. Post-stress analgesia was disturbed only in those rats with central amygdala injuries after intermittent shock exposition. This indicates differential involvement of dorsal basal and central nuclei in control of the anterior pituitary and pituitary-adrenocortical axis. It has been assumed that the central part of the amygdala processes unconditioned reinforcers, and the primary cues that occures in temporal proximity to the reinforcers, by augmenting neural and endocrine responses to their occurence. The basolateral complex is significant mostly in analysis of stimuli that acquire conditioned reinforcing properties. Therefore lesions of the structure change neither nonopioid neural nor opioid humoral forms of analgesia.

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THE ROLE OF THE NORADRENERGIC SYSTEMS IN THE REGULATION OF THE POST-CARBACHOL EMOTIONAL-DEFENSIVE REACTION IN CATS. Marek Wieczorek and Andrzej Romaniuk Department of Neurophysiology, University of L6di, 66 Rewolucji 1905r. St., 90-222 L6di, Poland The influence of the dorsal (DB) and ventral (VB) NA systems on post-carbachol defensive response

(PCR) and brain monoarnine content was investigated. The intensity of the PCR was determined by measuring the latency period of growling response (L), the total number of growls (N), the total time duration of separate growls (T) and the time duration of growling from the first to the last growl (D). After determination of control levels of these responses, DSP-4 (12gl21) was injected bilaterally in DB, VB and the medial forebrain bundle (MFB) respectively. Then we measured the intensity of the reaction 5, 10, 15 days after the DSP-4 lesion. Only after the DB lesions the was an increase in the intensity of the PCR observed. After the completion of the behavioural experiments, cats were killed by decapitation, and the levels of norepinephrine (NA), dopamine(DA), serotonin(5-HT), dihydroxyphenyl glicol (DOPAC), homovanilic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were measured using HPLC-ED in the anterior (AH) and posterior hypothalamus (PH), central grey mater (GC), amygdala (AM), hippocampus (HI) and frontal cortex (CO). It was found that DB lesions decreased the level of NA in the PH, GC, HI and CO and it also decreased 5-HIAA levels in the all areas. In all brain structures a decrease of the 5-HIAN5-HT ratio was observed as well. After VB lesions a decrease of NA levels occured in AH, PH, GC and AM. We also noted a decrease of 5-HT levels in the PH and GC and an increase of the 5-HIAN5- HT ratio in the PH and GC. After the MFB lesions, we observed a decrease of NA levels in AH, PH and HI, but no changes in the 5-HT system. These observations led us to the following conclusions: (1) the DB and VB are functionally differentiated and only DB participates in the regulation of the PCR in the cat, (2) functional interactions between the NA and 5-HT systems exist, i.e. DB in normal conditions has a tonic excitatory effect on 5-HT neurones, (3) the attenuation of the 5-HT system activity, in addition to the decrease of NA concentration in brain emotional structures, is a primary base for intensification of PCR following DB lesions .

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