Interaction of cholecystokinin and somatostatin with a selective μ-opioid agonist and μ- and κ- antagonists in thermoregulation

Abstract

We examined the effects of intracerebroventricular (i.c.v.) injections of cholecystokinin-octapeptide (CCK-8) and somatostatin (SST) and the interactions of these neuropeptides with the selective opioid antagonists, CTAP ( μ) and nor-BNI ( κ) and the μ-agonist, PL017, on body temperature (Tb) of the rat at normal ambient temperature (21±0.5°C). CCK-8 produced short-lasting (15–60 min), dose-related increases in Tb in a dose range of 20 to 900 ng but did not change the Tb at lower doses (0.1– 2 ng). Lower doses of SST (1 and 2 μg) produced hyperthermia (30–60 min) and a higher dose of SST (10 μg) caused hypothermia (30–45 min). PL017 (1 μg, i.c.v.), alone and in combination with CCK-8, produced hyperthermia. The CCK-8 (300 ng)-induced hyperthermia was blocked by pretreatment of rats with CTAP (1 μg, i.c.v.), suggesting that the higher doses of CCK-8 increase Tb through the interaction with μ-receptors or the enhancement of release of endogenous opioids acting on the μ-receptor. The hyperthermia elicited by a lower dose of SST (1 μg) was prevented by pretreatment with CTAP but not with nor-BNI (1 μg, i.c.v.). Pretreatment with nor-BNI blocked the higher dose (10 μg) of SST-induced hypothermia. PL017 or CTAP did not prevent the hypothermic effect of that dose of SST. These results indicate that a lower dose of SST (1 μg) stimulates the μ-receptor (directly or indirectly) and a higher dose (10 μg) interacts with the κ-receptor in regulation of Tb. Thus, the effects of both CCK-8 and SST on Tb appear to involve the endogenous opioid system.