directional interaction of midbrain and hypothalamus in the control of carbachol-induced aggression

AGGRESSIVE BEHAVIOR Volume 7, pages 131-144

Directional Interaction of Midbrain and Hypothalamus in the Control of Carbachol-Induced Aggression Cornelis L.J. Stokman and Murray Glusman New York State Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University

............................................................................................................ ............................................................................................................ Microinjection of carbachol into the ventromedial part of the anterior hypothalamus or the ventrolateral part of the mesencephalic central gray elicits affective aggression in the cat. Pretreatment with atropine in the same site blocks carbachol-induced aggression. Prior administration of atropine into the midbrain blocks aggression induced by carbachol injections into the hypothalamus, but atropine injected into the hypothalamus does not prevent affective aggression elicited by carbachol administered into the midbrain.

The results demonstrate a directional interaction between midbrain and hypothalamus, and provide suggestive evidence for a hierarchal organization of these limbic structures in the control of cholinergically-mediated affective aggression.

............................................................................................................ ............................................................................................................ Key words: aggression, carbachol, atropine, cholinergic blockade, hypothalamus,

midbrain, cat

INTRODUCTION

Aggressive behavior may be classified both on the basis of the eliciting stimuli and on the response patterns in which it is expressed. In the cat, at least two different types of aggression can be distinguished, affective and predatory. In affective aggression, biting and striking with the claws are accompanied by

Accepted for publication October 16, 1980.

Address reprint requests to Cornelis L.J. Stokman, Mid-Hudson Psychiatric Center, Box 158, New Hampton, NY 10958.

0096-140X/81/0702-0131$04.00 0 1981 Alan R. Liss, Inc.

132 Stokman and Glusman

strong autonomic responses such as piloerection and pupil dilatation, and by vocalizations such asgrowling and hissing [Hess, 1957; Wasman and Flynn, 19621 ; whereas predatory aggression is characterized by a stalking approach to the target, followed by biting and striking with minimal autonomic activation and little vocalization. Experimental evidence has shown that affective and predatory aggression are subserved by different neural pathways [Chi and Flynn, 19711, and probably also by different neurotransmitters [Goldstein, 1974; Myers, 19741 . Acetylcholine or its congener, carbachol, can elicit both types of aggression. Cholinergic stimulation of the ventral tegmental area of Tsai facilitates predatory aggression in the rat [ Bandler, 197 1 ] . Affective aggression can be induced by local microinjections in the hypothalamus, the amygdaloid complex, and the mesencephalic central gray [Myers, 1964,1974; Romaniuk & Golebiewski, 1977; Vahing et al, 19711. It can be blocked by prior systemic or local administration of a muscarinic blocking agent, atropine sulfate, but not by a nicotinic blocking agent, betamone, indicating that cholinergic aggression is mediated through pathways involving muscarinic rather than nicotinic receptors [Berntson and Leibowitz, 1973; Romaniuk et al, 19731. However, recently Romaniuk and Golebiewski [ 19771 reported a reduction in carbachol-induced aggression by pretreatment with hexamethonium, a specific nicotinic blocking agent, although to a lesser degree than by pretreatment with atropine. Carbachol-induced aggression can also be blocked by prior administration of norepinephrine or isoproter- inol in the same site, suggesting an interaction of cholinergic and adrenergic mechanisms in this type of aggression [Decsi et al, 19691.

we decided to study the possible interaction of these structures in the control of this behavior. We chose the hypothalamus and mesencephalic central gray as target areas, because injection of carbachol into these areas reliably induces aggression, and their involvement and mutual interaction in aggressive behavior have been implicated by physiological, anatomical, behavioral, and pharmacological studies [De Molina and Hunsperger, 1962; Proshansky and Bandler, 1975; Romaniuk and Golebiewski, 1977; Stokman and Glusman, 1976; Glusman, 19801.

Since carbachol can induce aggression in different sites of the limbic system,

METHODS AND MATERIALS

Five adult female cats (3-4 kg of bodyweight) were implanted, under sodium pentothal anesthesia, with chronic stainless steel guide cannulae (0.034 in outside diameter) aimed for the left medial anterior hypothalamus (AP: 12.5; Lat: 1 .O; Vert: 2.0; Jasper and Ajmone-Marsan, 1954) and for the left dorsal mesencephalic central gray (AP: 2.0; Lat: 1 .O; Vert: 4.0) by conventional stereotaxic techniques. A removable protective stylet (0.022 in diameter) was inserted into the guide cannulae and removed only during drug administration, when injection cannulae (0.01 6 in outside diameter) were inserted. Depending on the maximum

Limbic Control of Carbachol-Induced Aggression 133

sensitivity of the site of stimulation the tips of the injection cannulae extended 1 , 1.5,2.0,2.5, or 3.0 mm below the tips of the guide cannulae.

Following at least one week of postoperative recovery, carbachol (choline chloride carbamate), atropine (atropine sulfate), the vehicle control or sham injections were made into the ventromedial part of the anterior hypothalamus or into the ventrolateral part of the mesencephalic central gray. A sham injection consisted of removal of the stylet and insertion of the injection cannula, but without injection of any agent. This procedure was followed to control for possible mechanical tissue irritation and generation of small electrical currents. During vehicle control trials only the phosphate buffer (NaH2P04, 0.01 M and NazHP04, 0.01 M), which served as the solvent for the active agents, was injected. At all times a volume of 1 microliter of the isotonic solution was administered. The following carbachol concentrations were used: a) for hypothalamic injections: placebo, 5 , 10, 25, 50, 75, and 100 pg/pl, b) for midbrain injections: placebo, 1, 5, 10,25, 50, and 75 pg/pl. Atropine injections contained placebo, 20,40, or 80 pg of the active agent.

with a grid floor, which could be electrified. For each drug trial the tests for aggression were administered 30 minutes predrug, 30 minutes postdrug, and 3 hours postdrug. These times had been empirically determined to a) provide a stable predrug baseline, b) achieve the maximum behavioral drug effect, and c) ensure a return to predrug baseline. When two drugs or a combination of vehicle control (placebo) and drug were used, their administration was separated by 20 minutes. In such cases the tests for aggression were given 30 minutes before the first drug, 15 minutes after the first drug (placebo or atropine), 30 minutes, and 3 hours after the second drug. The test following the vehicle or atropine injection served to assess the behavioral effects of these agents alone, and was also used as the predrug baseline score for the second drug (carbachol).

Each subject received all seven concentrations, including placebo, twice. The sequence was randomized for each cat except that the same sequence could not be repeated for the same animal. The average score of the two runs was used as the datum for each subject.

The data in this paper are presented in terms of difference scores, ie, the difference in aggression score between the first postdrug test and the predrug test for that particular drug. Difference scores rather than absolute scores were chosen in order to adjust for individual differences in both baseline and carbachol- induced aggressive behavior. Student t-tests were used for statistical evaluation of the data.

The test for aggression and scoring procedure are a modified version of a Rating Scale for Agonistic Behavior, developed in our laboratory and described in detail previously [Glusman, 19741 . The modified rating scale is presented in Table I. Briefly, it consists of a standardized presentation of seven stimuli to

All behavioral testing was conducted in a Plexiglas chamber (94 X 56 X 76 cm)

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Limbic Control of Carbachol-Induced Aggression 13.5

the animals (electric foot shock, puff of air directed at face, lifting of limb, brushing of back, petting, brushing the abdomen, prodding), and the videotape recording of five possible agonistic responses (growling, hissing, biting, clawing, withdrawal). Aggression was operationally defined as the presence of one or more of the five agonistic responses to the test stimuli. These stimuli and responses were selected from a larger group following an item analysis, which had shown that they accounted for most of the variance. For each stimulus all responses were scored for presence or absence, and the final score for each test consisted of the weighted sum of these scores. The weights of each response had also been empirically determined by an item analysis. The tests were independently scored from videotape by two raters who were uninformed as to the nature of treat- ment the animal had received. As in our previous studies, interrater agreement was high (r = 0.95).

Upon completion of the experimental trials, the cats were sacrificed by intra- ventricular cardiac perfusion with 10% formalin. Frozen sections (30 p thick) of the excised brain were stained with cresyl violet acetate for cell identification, and with luxol fast blue for identification of fibers. Gross and microscopic examination of the sections was made to identify the location of the cannula tips.

RESULTS

Histological Analysis

Histological examination of the brains revealed that the most sensitive areas for eliciting carbachol-induced aggression were the ventromedial part of the anterior hypothalamus immediately rostra1 to the ventromedial nucleus, and the ventrolateral part of the mesencephalic central gray. Figure 1 presents photomicrographs of frontal brain sections of a representative hypothalamic (top) and mesencephalic (bottom) cannula placement. The cannula tips in all five subjects varied less than 1 mm in either vertical, lateral, or anterior direction. It should be noted that the injection cannulae extend 1-3 mm below the guide cannulae, and that, consequently, the sites of injection are 1-3 mm ventral to the cannula tips shown in the photomicrographs. These placements correspond well with sites from which chemical and electrical stimulation can elicit aggression [Flynn and Bandler, 1975; Romaniuk and Golebiewski, 19771. Also shown in this figure are the lesions that sometimes developed at the cannula tip after long periods of injections.

Aggression Induced by Carbachol Injections into the Hypothalamus and Midbrain

lnjection of carbachol into the ventromedial anterior hypothalamus induces an affective aggressive response in a dose-dependent fashion (Figure 2 , top). The larger the difference between postdrug and predrug score, the more intense


Fig. 1. Photomicrographs of frontal brain sections of a hypothalamic (top) and mesencephalic (bottom) cannula placement.

Limbic Control o f Carbachol-Induced Aggression 137

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Fig. 2. Dose-response function of carbachol-induced aggression in hypothalamus and midbrain (top) and blockade of carbachol-induced aggression by prior administration of atropine in the same site.


the carbachol-induced aggression. The aggressive responses of growling, hissing, biting, and clawing are accompanied by generalized autonomic reactions such as increased respiratory rate, pupil dilatation, piloerection, and salivation. The time course for the autonomic and behavioral responses is different. The autonomic responses typically start immediately following administration of carbachol, reach a maximum within 15 minutes, and return to predrug baseline within 60 minutes. The behavioral responses have a slower onset, reach a peak within 30 minutes, and return gradually to predrug baseline within 90 minutes. Among the behavioral responses vocalization (hissing and growling) appear first, followed by a more intense state of biting and clawing. The responses and time course are dose-dependent, very similar in most animals, and reproducible over time. However, following many drug trials larger amounts of carbachol may be needed to elicit the same degree of aggressive response.

The aggressive behavior increases initially with increases in amount of carbachol administered, followed at higher amounts by a decrease. We do not inter- pret this decline in aggression as a taming effect of carbachol at a higher dose. Instead, it reflects the emergence of strong autonomic responses and general activity that are imcompatible with the scoring of aggressive behavior in our testing situation.

Injection of carbachol into the ventrolateral part of the mesencephalic central gray induces similar aggressive behavior. However, the midbrain appears to be more sensitive to carbachol in eliciting aggression than is the hypothalamus. The average amount of carbachol needed to induce the maximum aggressive effect is 50 pg in the hypothalamus, whereas it is only 10 pg in the midbrain (Figure 2, top). The shorter response latencies following midbrain injections provide addi- tional evidence for the differential sensitivity.

tion into the midbrain or hypothalamus did not induce aggressive behavior, demonstrating the specificity of carbachol-induced aggression.

Administration of either the vehicle control (Figure 2 , top) or the sham injec-

Blockade of Carbachol-Induced Aggression by Pretreatment With Atropine in the Same Site

The effects of pretreatment with atropine, a muscarinic blocking agent, on carbachol-induced aggression are illustrated in Figure 2 (bottom). Microinjection of atropine (20 pg) in the same site 20 minutes prior to carbachol prevents carbachol-induced aggression both for midbrain and hypothalamus. Injection of atropine alone does not affect aggressive behavior, ie, the difference score is essentially zero. These data confirm previous results, and support conclusions by other investigators, that cholinergic aggression is mediated either exclusively [Baxter, 1967; Myers, 19741 or predominantly [Varszegi and Decsi, 1967; Romaniuk and Golebiewski, 19771 through muscarinic receptors.


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Directional Interaction of Midbrain and Hypothalamus in Carbachol-Induced Aggression

not only by atropine pretreatment in the same site (Figure 2 ) , but also by local microinjection of atropine in the ventrolateral part of the mesencephalic central gray (Figure 3). The cholinergic blockade of the midbrain to prevent choliner-

Aggression induced by carbachol injection in the hypothalamus can be blocked

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Fig. 3. Dose-dependent blockade of carbachol-induced aggression in hypothalamus by prior administration of atropine in the midbrain (top), and failure of atropine in the hypothalamus to block carbachol-induced aggression in the midbrain (bottom). AmCh: Injection of atropine into the midbrain, followed by carbachol into the hypothalamus. AhCm: Injection of atropine into the hypothalamus, followed by carbachol into the midbrain. A20, A40, A80 refer to 20,40, or 80pg of atropine. In all data points, five cats were used.


gically induced aggression in the hypothalamus is specific and dose-dependent, since prior administration of the vehicle in the midbrain does not prevent aggression induced by cholinergic stimulation of the hypothalamus (Figure 3 , bottom), and the degree of blockade increases with increased amount of atropine (20,40, and 80 pg). Twenty pg of atropine in the midbrain resulted in 64% reduction of aggression induced by carbachol injection into the hypothalamus (Figure 3, top). The reduction in aggression with pretreatment of 20 pg of atropine was signifi- cant (t = 2.63; df: 4; P < 0.05). In contrast, prior administration of the vehicle or atropine (20 pg) in the hypothalamus does not block aggression induced by administration of carbachol in the midbrain (t = 0.80; df: 4; P > 0.20).

DISCUSSION

The purpose of the present study was to investigate the interaction and rela- tive importance of two limbic structures, the hypothalamus and midbrain, in the control of cholinergically mediated affective aggression. The data allow US

to conclude that both structures, specifically the ventromedial part of the anterior hypothalamus and the ventrolateral part of the mesencephalic central gray, participate in the cholinergic control of aggression, and that muscarinic receptors are involved in the pathways of this behavior. Our results confirm and extend previous data, based on electrical and chemical stimulation, and lesion studies [De Molina and Hunsperger, 1962; Decsiet al, 1969; Stokman and Glusman, 1970; Romaniuk et al, 19731. Although most studies have implicated muscarinic rather than nicotinic receptors in mediating cholinergic aggression [ Baxter, 1967; Myers, 19741, several authors have suggested a nicotinic role as well [Decsi et al, 1969; Romaniuk and Golebiewski, 1977; Burov and Kurochkin, 1972, cited in Romaniuk and Golebiewski, 19771. While our study did not address this issue, our results are ip disagreement with Burovand Kurochkin [ 19721 who concluded that muscarinic receptors mediate aggression in the hypothalamus and hicotinic receptors aggression in the midbrain.

The main finding of our study is the ability of the midbrain to block aggression induced by carbachol injection into the hypothalamus, but not vice versa, providing evidence for a directional interaction of these limbic structures in the neurochemical control of affective aggression. Specifically, the functional integ- rity of the muscarinic receptors in the ventrolateral part of the central gray appears necessary for cholinergically mediated aggression to occur. Our conclusions, based on psychopharmacological evidence, support similar findings and suggestions of a hierarchal organization of the structures by De Molina and Hunsperger [1962], Ellison and Flynn [1968], and Berntson [1972] based on studies combining electrical stimulation and lesions.

Romaniuk and Golebiewski [ 19771 , reporting that prior bilateral administration of atropine in either midbrain or hypothalamus could prevent aggression induced by carbachol in both hypothalamus and midbrain, reject the hypothesis


that the midbrain is the main center in the control of aggressive behavior, and suggest instead that the midbrain and hypothalamus control aggressive behavior on the basis of a nonhierarchal rather than on a hierarchal relationship. Our finding of a directional interaction between midbrain and hypothalamus in the control of cholinergic aggression does not support their conclusions.

The discrepancy in findings could be explained alternatively by differences in 1) operational definition of aggression and response measures, ie, vocalization versus vocalization plus motor responses, 2) laterality, ie, bilateral versus unilateral injections, and 3) amounts of atropine needed in hypothalamus to block aggression induced by carbachol injections into the midbrain and vice versa. The last possibility seems quite plausible, especially in view of the differential sensitivity of these structures to carbachol in the elicitation of aggression (Fig. 2). Similar results were reported by Bandler [1975, 1979a, 1979bl , and Romaniuk and Golebiewski (19771 . However, the differential sensitivity of these structures to atropine has yet to be demonstrated.

Occasionally, we have observed in these and other cats with multiple cannulae in the midbrain, hypothalamus, and amygdaloid complex, that over long periods of time larger amounts of carbachol are needed to elicit the same degree of aggressive behavior, and that secondary lesions may develop ventral to the cannula tips. The decreased sensitivity to carbachol and the creation of small secondary lesions could be the result of either repeated passage of the injection cannula that may extend as much as 3 mm below the tip of the guide cannula, or due to pressure exerted by the injection of the solution.

Some cats with unilateral hypothalamic, mesencephalic, or amygdaloid cannulae, especially those subjects in which later histological analyses showed secondary lesions, gradually developed a spontaneous increase in aggressivity [Stokman and Glusman, 19761. We have also observed the same phenomenon in cats with unilateral electrolytic lesions in similar areas, specifically in the arcuate nucleus in the ventromedial part of the anterior hypothalamus [Stokman and Glusman, 19741. The aggressivity is more pronounced in response to stimuli presented contralateral to the lesion or cannula site. This laterality effect can be so strong, that touching a cat ipsilateral to the hypothalamic or mesencephalic lesion or cannula may elicit a purring response, whereas the same touch, contralaterally, will result in growling, hissing, biting, or striking (Stokman, unpublished data). Similar evidence for a contralateral receptive field for aggression has been reported by Edwards and Flynn [1972] and Flynn and Bandler [ 19751 . Our obser- vations, if confirmed by systematic investigation, would suggest that unilateral lesions involving the arcuate nucleus, may be sufficient for the development of permanent aggression, and that the VMH “savage” syndrome does not seem to require either bilateral lesions or involvement of the hypothalamic ventromedial nucleus [Wheatley, 19441.


While our finding that blockade of muscarinic receptors in the mesencephalic central gray can prevent aggression induced by carbachol injection into the hypothalamus but not vice versa demonstrates a directional interaction between these limbic structures in the control of affective aggression, it does not specify the anatomy of the cholinergic pathways involved [Decsi et al, 1969; Vahing and Allikmets, 19701. Nor does our study address the issue of the nature of the system, ie, whether the midbrain and hypothalamus are part of a descending system controlling aggression [De Molina and Hunsperger, 1962; Berntson, 1972; Proshansky and Bandler, 1975; Flynn, 19761 or an ascending system [Bandler, 1979b; Berntson et al, 1976; Siege1 and Edinger, 19781 or whether their differential thresholds in the elicitation of aggression simply reflect differences in compactness of the fibers within the medial forebrain bundle, ie, number of fibers per unit area [Bandler, 1979al.

ACKNOWLEDGMENTS

This research was supported in part by NIMH grants MY-3660 and MH-10315. The authors wish to express their appreciation and gratitude to Ms Ludmila Skaredoff for her expert assistance in all phases of this research.

REFERENCES

Bandler R (1 971 ): Chemical stimulation of the rat midbrain and aggressive behaviour.

Bandler R (1 975): Predatory aggression: Midbrain-pontine junction rather than hypo-

Bandler R ( 1 979a): Predatory attack behavior in the cat elicited by preoptic region

Nature 229:222-223.

thalamus as the critical structure? Aggressive Behavior 1 :261-266.

stimulation: A comparison with behavior elicited by hypothalamic and midbrain stimulation. Aggressive Behavior 5 :269-282.

Bandler R (1 979b): Centrally elicited aggressive behavior: A model system for the study of episodic neurobehavioral pathologies? Aggressive Behavior 5:

Baxter BL ( 1 967): Comparison of the behavioral effects of electrical or chemical 257-267

stimulation applied at the same brain loci. Experimental Neurology 19:412- 432.

cited aggressive behaviors in cats following midbrain lesions. Journal of Comparative and Physiological Psychology 8 1 :541-554.

muscarinic mediation. Brain Research 5 1 :366-370.

induced biting attack with natural predatory behavior in the cat. Journal of Comparative and Physiological Psychology 90: 167- 178.

brain structures of the cat in the achievement of rage reaction. (In Russian). ZH. Vyssh. Nerv. Deyat. 22: 13 1 1 - 13 13.

Berntson GG (1 972): Blockade and release of hypothalamically and naturally eli-

Berntson GG, Leibowitz SF ( 1 973): Biting attack in cats: Evidence for central

Berntson GG, Hughes HC, Beattie MS (1 976): A comparison of hypothalamically

Burov YV, Kurochkin JG( 1972): Possible participation of the N-cholinoreactive


Chi CC, Flynn JP (1 97 1 ): Neural pathways associated with hypothalamically elicited attack behavior in cats. Science 171 :703-706.

Decsi L, Varszegi MK, Mehes J (1 969): Direct chemical stimulation of various subcortical brain areas in unrestrained cats. In Lissak K (ed): “Recent Devel- opments of Neurobiology in Hungary.” Vol. 11. Budapest: Akademiai Kiado, pp 182-2 1 1.

governing defence and flight reactions in the cat. Journal of Physiology (London) 160:200-213.

Edwards SB, Flynn J P ( 1 972): Corticospinal control of striking in centrally elicited attack behavior. Brain Research 41 :51-65.

Ellison GD, Flynn J P (1968): Organized aggressive behavior in cats after surgical isolation of the hypothalamus. Archives Itallienner de Biologie 106: 1-20.

Flynn J P (1976): Neural basis of threat and attack. In Grenell R, Gabey S (eds): “Biological Foundation of Psychiatry.” New York: Raven Press, pp

Flynn JP. Bandler RJ (1 975): Patterned reflexes during centrally elicited attack

De Molina AF, Hunsperger RW (1 962): Organization of the subcortical system

273-295.

behavior. In Fields WS, Sweet WH (eds): “Neural Bases of Violence and Aggression.” St. Louis: Warren H. Green, Inc, pp 41-55.

Glusman M ( 1980): Brain Mechanisms in Aggression. Cahiers Internationaux Pinel. Revue de Psychiatrie et de Criminologie. Monographie, pp. 5-35.

Goldstein M (1 974): Brain research and violent behavior. Archives of Neurology 30:

Hess WR (1 957): “The Functional Organization of the Diencephalon.” New

Jasper H, Ajmone-Marsan C (1 954): “A stereotaxic atlas of the diencephalon of

Myers RD (1 964): Emotional and autonomic responses following hypothalamic

Myers RD (1 974): “Handbook of Drugs and Chemical Stimulation of the Brain.

1-34.

York: Grune and Stratton.

the cat.” Ottawa: National Research Council of Canada.

chemical stimulation. Canadian Journal of Psychology 18:6-14.

Behavioral, Pharmacological and Physiological aspects.” New York: Van Nostrand Reinhold Company, 759 pp.

control of aggressive behavior. Aggressive Behavior 1: 135-1 55.

cal behavior. In Whalen R, Thompson R, Verzeano M, Weinberger N (eds): “The Neural Control of Behavior.” New York: Academic Press, pp 175-206.

Romaniuk A, Brudzynski S, Gronska J (1973): The effect of chemical blockade of hypothalamic cholinergic system on defensive reactions in cats. Acta Phy- siologica Polonica 24:809-8 16.

in expression of aggressive behavior in cats. Acta Neurobiological Experimen- talia 37:83-97.

Siege1 A, Edinger H ( 1 978): Neural control of aggression and rage behavior. In Morgane JP, Panhseep J (eds): “The Hypothalamus.”

Stokman CLJ, Glusman M ( 1 970): Amygdaloid modulation of hypothalamic flight in cats. Journal of Comparative and Physiological Psychology 71 :365-375.

Stokman CLJ, Glusman M ( 1 974): Effects of dopa and imipramine on agonistic behavior induced by hypothalamic lesions in cats. Federation Proceedings 33:464.

Proshansky E, Bandler RJ (1 975): Midbrain-hypothalamic interrelationships in the

Roberts WW (1970): Hypothalamic mechanisms for motivational and species typi-

Romaniuk A, Golebiewski H (1977): Midbrain interaction with the hypothalamus


Stokman CLJ, Glusman M (1 976): Interaction of limbic structures in the control of

Vahing VA, Allikmets LH (1 970): Behavioural and visceral reactions elicited by cholinergic rage. Neuroscience Abstracts 2: 801.

chemical stimulation of the hypothalamus and septum in cats. Sechenov Physiol- ogy Journal (USSR) 56:38-47.

Vahing VA, Mehilane LS, Allikmets LH ( 1 97 1): Neurochemical analysis of hypothalamic and midbrain effector centers regulating emotional behavior. Jour- nal of Higher Nervous Activity 21 :551-558.

Varszegi MK, Desci L (1 967): Some characteristics of the rage reaction evoked by chemical stimulation of the hypothalamus. Acta Physiologica Academica Scientifica Hungaria 32:61-68.

Wasman M, Flynn JP (1962): Directed attack elicited from hypothalamus. Ar- chives of Neurology 6: 220-227.

Wheatley MD (1 944): The hypothalamus and affective behavior in cats.: A study of effects of experimental lesions with anatomic correlation. Archives of Neurology and Psychiatry 52:296-3 16.

directional interaction of midbrain and hypothalamus in the control of carbachol-induced aggression

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