CHOLECYSTOKININ MODULATES THE AVERSIVE COMPONENT OF MORPHINE-WITHDRAWAL SYNDROME IN RATS

The conditioned place aversion paradigm was used to investigate the ro le of cholecystokinin in the aversive/dysphoric component of morphine abstinence. Several cholecystokinin ligands were chronically administe red during the development of morphine dependence: the CCKA antagonist devazepide, the CCKB antagonists PD-134,308 and L-365,260, and the CC KB agonist BC 264. The CCK-B antagonists L-365,260 and PD-134,308 decr eased and completely blocked (respectively) the place aversion induced by naloxone in morphine dependent animals whereas BC 264 and devazepi de were inactive in this model. No effect was observed in non-dependen t animals after chronic administration of these CCK-ligands. These res ults show a distinct role for CCK receptors in the regulation of the m otivational component of morphine abstinence, probably related to thei r differential effects in the regulation of limbic dopaminergic neuron s. (C) 1998 Published by Elsevier Science ireland Ltd.