Opposing effects of CCK(A) and CCK(B) antagonists on the development of conditioned activity in rats

Cholecystokinin (CCK) is co-localized with dopamine (DA) in portions of the mesolimbic system. Evidence suggests that CCK(B) receptor mechanisms mediate an inhibitory effect on DA function while CCK(A) receptor mechanisms mediate a facilitory effect on DA function. As DA has been implicated in the acquisition of conditioned activity, the present experiments investigated the interaction between selective CCK(A) and CCK(B) receptor antagonists on the development of conditioned activity. Experiment 1 determined whether the CCK(B) receptor antagonist, L-365,260 (0.01, 0.1 and 1.0mg/kg, i.p.) would induce conditioned activity. Paired groups received four two-hour drug-environment pairings whereas Unpaired groups received the two stimuli explicitly unpaired. The group that received L-365,260 (0.mg/kg) paired with the test environment subsequently showed increased activity in that environment in a drug-free test day. Experiment 2 examined the interaction of pre-treatment with the CCK(A) receptor antagonist, devazepide (0, 0.001, 0.01 and 0.1mg/kg) on the conditioned activity induced by L-365,260 (0.1mg/kg). Devazepide impaired the acquisition of L-365,260 conditioned activity. These studies suggest that CCK mechanisms play a key role in the development of conditioned activity and extend previous research suggesting a bi-directional function for CCK(A) and CCK(B) receptors.