Increased endogenous levels of neuropeptide Y in specific hypothalamic regions of rats with spontaneous hyperphagia

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    INVOLVEMENT OF ENDOGENOUS OPIOIDS IN WATER INTAKE OF GENETICALLY POLYDIPSIC MICE. TOSHIHIKO KATAFUCHI I, YUKIO }IATTORI 2, KIY03|I KOIZUM1.3, Departments of Physlolo~y, IFaculty of Medicine, Kyushu University, Fukuoka, 812, 20kayama University Medl- cal School, Okayama, 700, Japan, and ~State University of New York, Health Science Center at Brooklyn, Brooklyn NY 11203, USA.

    Effects of oplold antagonists on the genetlc polydlpsia of the STR/N strain of mice were investigated. Naltrexone (NLTX, 0.5-5.0 mg/kg) Injected subcutaneously before dark period attenuated spontaneous drinking for the first 3 h after injec- tion only In the inbred polydlpsle mice (STR/N), whose water intake was 5 times that of controls (non-polydlpslc mutant, STR/IN. and Swlss/Webster mice). The highest dose (S mg/kg) of NLTX administration reduced drinking also during the next 3-6 h period and overnlght feeding. Lateral cerebroventrlcular (Icy) injec- tion of NLTX, 1.0 and 2.5 ~ff (per mouse), suppressed drlnking only in the poly- dlpslc mice, while the higher dose (5.0 ag) attenuated drlnklng and feeding of both the polydlpslc mice and their controls. However, Icy injection of specific -receptor antagonist, nor-blnaltorphlmine (nor-BNI, 0.5-2.5 ~ g), suppressed

    drinking only in the polydlpslc strain of mlce at one half dose of that needed for NLTX. Furthermore, even a higher dose of nor-BNI administration was without effect on food intake In all strains. These findings suggest that the central oploid system plays an Important role in causing the polydlpsla in the STR/N mice. probably through the x oplold receptor.

    SENSITIVITY TO OPIOIDS OF NEURONS IN THE ANTEROVENTRAL THIRD VENTRICLE REGION OF POLYDIPSIC INBRED MICE. YUKIO HATTORII t TOSHIHIKO KATAFUCHI 2 , AND KIYOMI KOIZUMI3f IDepartment of Physiology r Okayama University Medical School r Okayama 700, Japan, 2Department of Physiology r Faculty of Medicine r Kyushu University r Fukuoka 812 r Japan r and 3Department of Physiology, State University of New York t Health Science Center at Brooklyn, New York 11203 r U.S.A.

    Responsiveness of neurons in the anteroventral third ventricle region (AV3V) to morphine and opioid peptides was investigated in slice preparations of genetically polydipsic mice, STR/N, and non-polydipsic control mice, Swiss/Webster (S/W). Morphine inhibited AV3V neurons of the STR/N and the S/W, in which the morphine-sensitive neurons were not affected by angiotensin II. In these mice, AV3V neurons were inhibited by opioid agonists for three receptor types: the mu agonist [D-AIa 2, N-Me-Phe 4 , Gly5-ol]-enkephalin (DAGO), the delta agonist [D-Pen 2,5 ]-enkephalin (DPDPE), and the kappa agonist dynorphin A(I-13) (DYN). Of these opioid agonists, DAGO was most potent in inhibiting AV3V neurons, followed in order by DYN and DPDPE. The proportion of neurons inhibited by the opioids, especially by DYN, was lower in the STR/N than in the S/W. The threshold concentration of the opioids for inhibiting AV3V neurons was higher in the STR/N than in the S/W. The inhibitory actions of the opioids were reversibly blocked by naloxone, and persisted under synaptic blockade. These results suggest that the opioid system in the AV3V is involved in the genetic polydipsia of STR/N mice.

    INCREASED ENDOGENOUS LEVELS OF NEUROPEPTIDE Y IN SPECIFIC HYPOTHALAMI~ REGIONS OF RATS WITH SPONTANEOUS HYPERPHAGIA. TAKASHI SHIMAZU, AND MITSUSHI ABE , Department of Medical Biochemistry, Ehime University School of Medicine, Shigenobu, Ehime 791-02, Japan.

    Neuropeptide Y (NPY) is a potent stimulant of feeding behavior when administered either into the paraventricular hypothalamic nucleus (PVN) or the lateral ventricle. We have investigated whether endogenous level of NPY in the hypothalamus may be modified under some pathological state with increased eating drive. NPY concentration was determined by radioimmunoassay in discrete hypothalamic regions microdissected from fresh brain slices of obese, hyperphagic rats and different types of diabetic, hyperphagic rats. In obese hyperphagic Zucker rats, NPY concentrations were significantly increased in the arcuate nucleus (ARH) and the ventromedial hypothalamic nucleus (VMH) when compared with lean controls. In spontaneously diabetic and hyperphagic rats such as the BB and Wistar fatty rats, NPY concentrations were also high in the PVN and ARH as compared to respective controls. Moreover, in streptozotocin-induced diabetic hyperphagic rats, elevated NPY contents in the PVN and ARH returned to the normal level with amelioration of the syndrome after insulin treatment. These data suggest that hyperphagia seen in some pathologic state of rats is attributable to increased hypothalamic NPY and that NPYergic neuron in the ARH-PVN system participates in the regulation of energy balance.

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