EFFECTS INDUCED BY BC-264, A SELECTIVE AGONIST OF CCK-B RECEPTORS, ONMORPHINE-DEPENDENT RATS

The aim of this study was to investigate the possible interaction betw een neuronal cholecystokinin (CCK) and opiate dependence. Rats were ma de dependent to morphine and the ability of cholecystokinin-octapeptid e (CCK-8) and Tyr(SO3H)-gNle-mGly-Trp-(NMe)Nle-Asp-Phe-NH2 (BC 264), a selective agonist of CCK-B receptors, to induce signs of morphine wit hdrawal after ICV injection was tested. Behavioral responses were comp ared to those occuring during the naloxone-precipitated morphine withd rawal syndrome. In contrast to naloxone, CCK-8 (0.1, 1, and 10 mu g, I CV) did not precipitate any sign of withdrawal. BC 264 (0.1, 1, and 10 mu g, ICV) induced a strong hyperlocomotion and wet dog shakes in mor phine-dependent rats, the latter effect also observed in nondependent animals. In rats receiving acute morphine, BC 264 induced an opposite effect (i.e., blockade of morphine-induced hyperactivity). Taken toget her, these results suggest that CCK plays only a minor role in the exp ression of morphine physical dependence.