Examining the role of cholecystokinin in appetitive learning in the infant rat

The role of Cholecystokinin (CCK), a gut hormone and neuropeptide, in early learning was examined. Pairing a novel odor (presented away from the nest) with exogenously administered CCK (0.25 & 0.5 μg/kg IP) has been shown to produce a conditioned-odor preference in infant rats (Weller, A.; Blass, E.M. Behav. Neurosci. 104:199-206; 1990). This suggests that CCK can act as a positive unconditioned stimulus (UCS). In the present study the possibility that CCK mediates learning was examined in 12-day-old rats, using rewards that represent aspects of the dam and the nest. In Experiments 1 and 2, pups received the selective CCK1 receptor antagonist devazepide (600 μg/kg), the selective CCK2 receptor antagonist L365,260 (600 μg/kg), or vehicle. In a series of training trials, choosing a particular floor texture was rewarded by 20 sec. on a rug texture (experiment 1) or with maternal (feces) odor (experiment 2). In experiment 3, after administering devazepide (0, 600, or 1000 μg/kg) a novel odor was paired once with reunion of the pup with its dam. The dependent measure in all studies was the pup's relative preference toward the (tactile or olfactory) conditioned stimulus (CS), determined in preference tests. Conditioned preferences were evident in all experiments. The CCK receptor antagonists did not increase conditioned preference levels. L365, 260 (experiment 2) and devazepide (experiment 1) clearly blocked the appearance of the conditioned effect in one of the experiments. In addition, devazepide treatment eliminated the conditioned effect in the two other experiments, by increasing preference levels in the control groups. In summary, the results suggest that endogenous CCK mediates some aspects of the infant's acquisition of new associations. The role of the two receptor-subtypes appears to be different, depending on the context and the nature of the rewarding stimulus.