Devazepide, a CCKA receptor antagonist, impairs the acquisition of conditioned reward and conditioned activity.
Cholecystokinin (CCK) is co-localized with dopamine (DA) in portions of the mesolimbic system, where it may facilitate the function of DA through the CCKA receptor subtype. DA has been implicated in the acquisition of conditioned incentive learning, raising the possibility of a role for endogenous CCK in this learning process. This hypothesis was tested using two complementary behavioral paradigms. Experiment 1 examined the effects of systemic administration of the CCKA receptor selective antagonist, devazepide (0, 0.001, 0.01, 0.1 mg/kg), on the acquisition of conditioned reward. Two novel levers were presented to drug-free animals in a test session; depression of the conditioned reward (CR) lever produced a light-tone stimulus previously paired with food availability while depression of the non-CR lever produced no programmed consequence. Animals receiving vehicle pretreatment in the food-CS conditioning sessions responded more frequently on the CR lever during the 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 acquisition of conditioned reward. In contrast, experiment 2 showed that the development of conditioned reward was not affected by similar administration 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 acquisition of conditioned activity induced by amphetamine were assessed in experiment 5. During four conditioning sessions, rats received devazepide (0, 0.001, 0.01, 0.1 or 1.0 mg/kg) treatment prior to amphetamine-environment pairings. The conditioned activity effect was demonstrated if on the subsequent drug-free test day the environment alone elicited increased locomotion. Devazepide (0.1 or 1.0 mg/kg) attenuated the development of conditioned activity. Together, these results provide converging evidence that intact CCKA function may be necessary for the development of conditioned incentive learning.
Josselyn
S A
SA
Department of Psychology, University of Toronto, Ontario, Canada.
Franco
V P
VP
Vaccarino
F J
FJ
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D020109:Devazepide; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D013997:Time Factors
D001570:Benzodiazepinones; D006727:Hormone Antagonists; D011949:Receptors, Cholecystokinin; D020109:Devazepide