Pharma('oh)gvBio('hemistry & B~'harior, Vol. I I. pp. 473~177. Printed in the U.S.A. Neurotensin: Distribution of Hypothermic Response in Mammalian and Submammalian Vertebrates ARTHUR J. PRANGE, JR., CHARLES B. NEMEROFF, GARTH BISSETTE, PAUL J. MANBERG, ALBERT J. OSBAHR, III, GORDON B. BURNETT, PETER T. LOOSEN AND GARY W. KRAEMER* ,~iologieal Sciences Research Center Department oJ'Psychiatt3' and The Neurobiology Program. University q[" North Carolina. School of Medicine Chapel Hill, NC 27514 and *Primate Laboratot3' and Wisconsin Psv('hiatric Resear('h Institute, University of Wisconsin S~'hool (?/'Medicine, Madison. WI 53206 Received 4 April 1979 PRANGE, A. J., JR.. C. B. NEMEROFF, G. BISSETTE. P. J. MANBERG, A. J. OSBAHR. I11. G. B. BURNE'FI. P. T. LOOSEN AND G. W. KRAEMER. Net~rotensin: distrih,tion q/'l~yt)oth~,rlni( ' re,v)optse in mdmmdli~ttl and stlhm(ltnmdlittlt ,'~'rtehrat~,,L PHARMAC. BIOCHEM. BEHAV. 11(5) 473~,77. 1979.--Neurotensin (NT). an endogenous tridecapeptide (pGlu-l,eu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-lle-Leu-OH), is a potent hypothermic agent after central administration in the mouse and rat. The purpose of the present investigation was to evaluate the effect of NT on thermoregulatory processes in a variety of mammalian and non-mammalian vertebrates: bluegill, frog, lizard, pigeon, ground squirrel, woodchuck, golden hamster, rabbit, guinea pig, gerbil, mouse, rat and monkey. All species except monkey were tested in two ambient environmental temperatures. 23°C and 4°C, except poikilotherms. Animals were injected intracisternally with microgram quantities of NT or vehicle, and body temperature was periodically assessed over a 2 hr period. N'r did not induce a significant alteration in body temperature in any of the poikilotherms studied (bluegill, frog. and lizard). At 23~C NT produced a significant hypothermic response in the mouse, rat, gerbil, and monkey with no effect observed in the pigeon, rabbit, guinea pig. golden hamster, ground squirrel or woodchuck. At 4°C, NT produced a significant decrease in body temperature in the mouse, rat. gerbil, guinea pig and golden hamster with no effect evident in the pigeon, rabbit. ground squrrel or woodchuck. Species known to respond to cold by increasing metabolic rate (e.g. mouse and rat) appear to be most responsive to NT. The hypothermic activity of NT in a '.ariety of mammals suggests that the peptide may play a role in thermoregulation. Neurotensin Thermoregulation Neuropeptides Hypothermia Hibernators N EUROTENSIN (NT) is a tridecapeptide, pGlu-Leu-Tyr- Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-lle-Leu-OH 15,41. Radio- immunoassay and immunohistochemical techniques have been used to identify NT in gut 110,16] and brain [16, 21,221. When injected peripherally it causes vasodilation, hypoten- sion. increased vascular permeability and transient cyanosis 11.4, 51. After peripheral injection certain endocrine effects also have been noted, including hyperglycemia [2, 7, 13] and the release of a variety of anterior pituitary hormones [4, 12, 191. When injected directly into the cerebroventricular sys- tem, NT causes hypothermia in rats and mice 11, 3, 141. Recently intracisternally (IC) administered NT has been reported to exert antinociceptive effects in mice [81. Di- minished locomotion and extension of barbiturate narcosis h~tve also been noted after central administration, but these effects may be attributable to the hypothermic action of NT [1.41. Given peripherally, even large doses of the peptide exert no effects on body temperature [ 14] or nociception [81, suggesting that the blood-brain ban'ier effectively excludes this substance. Since the discovery of the hypothermic effect of NT, studies have revealed that the C-terminal end of the molecule is essential for this action I111. NF-induced hypothermia appears not to depend upon the integrity of brain cholinergic. noradrenergic, or serotonergic neural systems 115,181. to further explore the possible physiological role of NT in thermoregulation we have studied its effects after central administration in a variety of species, and this is the subject of the present report. METHOD Representatives from 13 species were selected for study (]'able 1), at least one from each of the vertebrate classes. (The species tested were as follows: bluegill, Lepomis mac- rochirus: frog, Rana pipiens: lizard, Anolis carolenensis: pigeon, Columba domestica" ground squirrel, Citellus tridecalineatus: woodchuck, Marmota monax, golden hams- ter, Mesocricetus auratus: rabbit, Oryctolagus cuniculus: guinea pig, Cavia porcellus: gerbil. Gerbillus gerbillus: Copyright ~:' 1979 ANKHO International Inc.--0091-3057/79/110473-04501.00/0