Cholecystokinin is necessary for the expression of morphine conditioned place preference

There is evidence that the neuropeptide cholecystokinin (CCK) is important for the rewarding effects of drugs of abuse. However, less is known regarding the role of CCK in drug seeking and craving. The present study investigated whether the CCKB antagonist L-365, 260 could block morphine-induced drug seeking using the conditioned place preference paradigm and whether the dopaminergic reward pathway contributes to the effect of L-365, 260 on expression of morphine place preference. We found that systemic administration of the CCKB antagonist L-365, 260 attenuates the expression of morphine-induced drug seeking as assessed using conditioned place preference (CPP) and shows that this effect is mediated by CCKB receptors in the anterior nucleus accumbens (NAcc). Additionally, we demonstrate that this effect is dependent on D2 receptor activation in the anterior nucleus accumbens (NAcc). These results indicate that endogenous CCK modulates the incentive-salience of morphine-associated cues and suggest that CCK antagonists may be useful in the treatment of drug craving.