Effects induced by BC 264, a selective agonist of CCK-B receptors, on morphine-dependent rats

The aim of this study was to investigate the possible interaction between neuronal cholecystokinin (CCK) and opiate dependence. Rats were made dependent to morphine and the ability of cholecystokinin-octapeptide (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 withdrawal after ICV injection was tested. Behavioral responses were compared to those occurring during the naloxone-precipitated morphine withdrawal syndrome. In contrast to naloxone, CCK-8 (0.1, 1, and 10 micrograms, ICV) did not precipitate any sign of withdrawal. BC 264 (0.1, 1, and 10 micrograms, ICV) induced a strong hyperlocomotion and wet dog shakes in morphine-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 together, these results suggest that CCK plays only a minor role in the expression of morphine physical dependence.