DEVAZEPIDE, A CCKA RECEPTOR ANTAGONIST, IMPAIRS THE ACQUISITION OF CONDITIONED REWARD AND CONDITIONED ACTIVITY

Cholecystokinin (CCK) is co-localized with dopamine (DA) in portions o f the mesolimbic system, where it may facilitate the function of DA th rough the CCKA receptor subtype. DA has been implicated in the acquisi tion of conditioned incentive learning, raising the possibility of a r ole for endogenous CCK in this learning process. This hypothesis was t ested using two complementary behavioral paradigms. Experiment 1 exami ned the effects of systemic administration of the CCKA receptor select ive antagonist, devazepide (0, 0.001, 0.01, 0.1 mg/kg), on the acquisi tion of conditioned reward. Two novel levers were presented to drug-fr ee animals in a test session; depression of the conditioned reward (CR ) lever produced a light-tone stimulus previously paired with food ava ilability while depression of the non-CR lever produced no programmed consequence. Animals receiving vehicle pretreatment in the food-CS con ditioning sessions responded more frequently on the CR lever during th e test session. However, pre-treatment with devazepide (0.1 mg/kg but not 0.001 or 0.01 mg/kg) in the conditioning sessions blocked the acqu isition of conditioned reward. In contrast, experiment 2 showed that t he development of conditioned reward was not affected by similar admin istration of the CCKB selective antagonist, L-365,260 (0, 0.001, 0.01 or 0.1 mg/kg). The possibilities that devazepide (0.1 mg/kg) impaired the development of conditioned reward by decreasing the amount of food consumed or by inducing a conditioned taste aversion to the food were ruled out in experiments 3 and 4. The effects of devazepide on the ac quisition of conditioned activity induced by amphetamine were assessed in experiment 5. During four conditioning sessions, rats received dev azepide (0, 0.001, 0.01, 0.1 or 1.0 mg/kg) treatment prior to amphetam ine-environment pairings. The conditioned activity effect was demonstr ated if on the subsequent drug-free test day the environment alone eli cited increased locomotion. Devazepide (0.1 or 1.0 mg/kg) attenuated t he development of conditioned activity. Together, these results provid e converging evidence that intact CCKA function may be necessary for t he development of conditioned incentive learning.