Brain Research, 128 (1977) 485-496 485 O Elsevier/North-Holland Biomedical Press NEUROTENSIN: CENTRAL NERVOUS SYSTEM EFFECTS OF A HYPO- THALAMIC PEPTIDE CHARLES B. NEMEROFF, GARTH BISSETTE, ARTHUR J. PRANGE, JR., PETER T. LOOSEN, T. STEVEN BARLOW and MORRIS A. LIPTON Departments of Psychiatry and Anatomy, The Neurobiology Program, Biological Sciences Research Center, University of North Carolina School of Medicine, Chapel Hill, N. C. 27514 (U.S.A.) (Accepted October 11th, 1976) SUMMARY The central administration of neurotensin, an endogenous hypothalamic tri- decapeptide, produces a marked dose-related decrease in body temperature of mice and rats at an ambient temperature of 25 °C. This effect is even more pronounced when mice are placed at 4 °C to increase the rate of decline of body temperature. Other sequelae observed after central administration of neurotensin are decreases in locomotor activity in rats and a marked dose-related enhancement in pentobarbital- induced mortality, sedation and hypothermia. This latter effect was shown to be due to a significant reduction in the metabolic degradation of the barbiturate. None of the above-mentioned effects are observed after peripheral neurotensin administration, suggesting that this peptide does not readily cross the blood-brain barrier. Neuro- tensin appears to be one of a growing list of neuropeptides that can affect CNS function. INTRODUCTION Neurotensin is a tridecapeptide (pGlu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro- Tyr-Ile-Leu-OH) that was first isolated by Carraway and Leeman from bovine hypothalamus 8,1°. Immunoreactive neurotensin has also been shown to be present in the hypothalami of a variety of species including rat, mouse, rabbit, and man 9. Several studies~,4,5,20, ~1 have shown that peptides can modify the sedative and hypothermic properties of barbiturates and other centrally acting depressants. In this study the effects of peripherally and centrally administered neurotensin on pentobarbital-induced narcosis and hypothermia were investigated. This led to the study of the effect of intracisternal (i.c.) neurotensin on the disposition and meta- bolism of [3H]pentobarbital. In addition the effect of i.v. and i.c. neurotensin on