Interaction of cholecystokinin and somatostatin with a selective mu-opioid agonist and mu- and kappa-antagonists in thermoregulation

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(mu) and nor-BNI(kappa) and the mu-agonist, PL017, on body temperature (Tb) of the rat at normal ambient temperature (21+/-0.5 degrees 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 mu g) produced hyperthermia (30-60 min) and a higher dose of SST(10 mu g) caused hypothermia (30-45 min). PL017 (1 mu g, 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 mu g, i.c.v.), suggesting that the higher doses of CCK-8 increase Tb through the interaction with mu-receptors or the enhancement of release of endogenous opioids acting on the mu-receptor. The hyperthermia elicited by a lower dose of SST (1 mu g) was prevented by pretreatment with CTAP but not with nor-BNI(1 mu g, i.c.v.). Pretreatment with nor-BNI blocked the higher dose (10 mu g) 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 mu g) stimulates the mu-receptor (directly or indirectly) and a higher dose (10 mu g) interacts with the mu-receptor in regulation of Tb. Thus, the effects of both CCK-8 and SST on Tb appear to involve the endogenous opioid system.