Evaluation of neurotensin's thermolytic action by ICV infusion with receptor antagonists and a Ca++ chelator.

To investigate the mechanisms responsible for the thermolytic action of neurotensin (NT), cannulae for intracerebroventricular (ICV) injection were implanted stereotaxically in Sprague-Dawley rats. Postoperatively, body temperature in the unrestrained rat was monitored continuously by a colonic thermistor probe. NT in a dose of 1.5-4.5 micrograms or CSF carrier vehicle was infused bilaterally in the cerebral ventricle (ICV) in a volume of 7.5 microliters. With the rats kept at an ambient temperature of 22 degrees C, NT given ICV produced a dose-dependent fall in core temperature of greater than 0.8 degree C. Pre-treatment of the animal's cerebral ventricle with amine receptor antagonists, phentolamine (20.0 micrograms), butaclamol (10.0 micrograms), methysergide (20.0 micrograms) or atropine (25.0 micrograms), all similarly infused ICV, failed to alter the hypothermia induced by NT. However, the calcium chelating agent, EGTA, given ICV in a dose of 4.0-8.0 micrograms blocked the thermolytic effect of NT on body temperature in a concentration-dependent manner. These results suggest that the central thermolytic action of NT is not mediated by catecholamine or other aminergic pathways which are implicated in the central mechanisms of thermoregulation. Rather, the peptide may act on a cellular process involving calcium activity in the hypothalamus, presumably to impair the maintenance of the animal's "set-point" for body temperature.