Opiate Antagonistic Function of Cholecystokinin in Analgesia and Energy Balance Systemsa

Abstract

Because several effects of cholecystokinin (CCK) are opposite to those reported for opioids, it seemed likely that CCK may function as an endogenous antagonist of opiate action. This hypothesis was tested initially by assessing the effect of CCK on opiate analgesias. Systemic administration of CCK attenuated opiate analgesias produced by morphine and footshock, but did not reduce nonopiate footshock analgesia. When delivered directly to the lumbosacral spinal cord, a critical site of opiate action, 3.6 ng of CCK-8 significantly inhibited opiate-mediated footshock analgesia; however, 3.6 ng of desulfated CCK-8 did not have an effect. Sequestering of endogenously circulating CCK by antibodies raised against CCK through an active immunization procedure resulted in a potentiation of morphine analgesia. If CCK functions to inhibit opiate involvement in behaviors other than pain responsitivity, CCK-induced satiety may result from an inhibition of opiate-stimulated feeding. In immunohistochemical studies, we have found a dense CCK fiber plexus in the dorsal PVN, a critical site for opiate-induced feeding. Direct microinjections of CCK to this region reduced short-term food intake by 28%. The findings presented here support the hypothesis that an opiate antagonistic function of CCK may account for several previously reported effects of this peptide.