Neurotensin-induced hypothermia: evidence for an interaction with dopaminergic systems and the hypothalamic--pituitary--thyroid axis.
Neurotensin (NT), an endogenous tridecapeptide, produces significant hypothermia after intracisternal (i.c.) or intracerebroventricular (i.c.v.) administration in microgram quantities in a variety of laboratory animals. The present study sought to clarify the mechanism of the hypothermic action by utilizing pharmacological treatments which alter the function of brain neurotransmitter systems. Pretreatment of rats with anti-muscarinic (atropine), anti-noradrenergic (propranolol, a beta-blocker; phenoxybenzamine, an alpha-blocker) or anti-opiate (naloxone) agents did not significantly alter NT-induced hypothermia. Similarly depletion of brain serotonin (5-HT) with parachlorophenylalanine did not affect NT-induced hypothermia. However, depletion of brain catecholamine content with 6-hydroxydopamine resulted in a significant potentiation of NT-induced hypothermia as did pretreatment with haloperidol, a dopamine (DA) receptor antagonist. Furthermore, in rats with selective depletions of brain DA, but not norepinephrine (NE), NT-induced hypothermia was significantly augmented. Thus an interaction between brain DA systems and NT appears likely. These data indicate that NT-induced hypothermia is not dependent on intact functional activity of NE, 5-HT, muscarinic ACh or endogenous opiate systems but suggests interactions between brain DA circuits and NT. In other experiments, NT-induced hypothermia was found to be antagonized significantly by i.c. injection of thyrotropin-releasing hormone (TRH), but not by pretreatment with L-triiodothyronine. Another endogenous tripeptide (Pro--Leu--Gly--NH2, MIF-I) had no effect. Thyroidectomy (THX) significantly potentiated NT-induced hypothermia; NT administered i.c. significantly reduced the high serum TSH levels of THX rats. Thus, NT and TRH, two endogenous peptides, appear to be antagonists in certain systems.
D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D010134:Fenclonine / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D006892:Hydroxydopamines / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008297:Male; D009496:Neurotensin / Q000494:pharmacology*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*; D013961:Thyroid Gland / Q000187:drug effects*; D013972:Thyrotropin / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology
D006892:Hydroxydopamines; D011954:Receptors, Dopamine; D014284:Triiodothyronine; D009496:Neurotensin; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin; D006220:Haloperidol; D010134:Fenclonine