Competition between novelty and cocaine conditioned reward is sensitive to drug dose and retention interval

Abstract

The conditioned rewarding effects of novelty compete with those of cocaine for control over choice behavior using a place conditioning task. The purpose of the present study was to use multiple doses of cocaine to determine the extent of this competition and to determine whether novelty's impact on cocaine reward was maintained over an abstinence period. In Experiment 1, rats were conditioned with cocaine (7.5, 20, or 30 mg/kg ip) to prefer one side of an unbiased place conditioning apparatus relative to the other. In a subsequent phase, all rats received alternating daily confinements to the previously cocaine paired and unpaired sides of the apparatus. During this phase, half the rats had access to a novel object on their initially unpaired side; the remaining rats did not receive objects. The ability of novelty to compete with cocaine in a drug free and cocaine challenge test was sensitive to cocaine dose. In Experiment 2, a place preference was established with 10 mg/kg cocaine and testing occurred after 1, 14, or 28 day retention intervals. Findings indicate that choice behaviors mediated by cocaine conditioning are reduced with the passing of time. Taken together, competition between cocaine and novelty conditioned rewards are sensitive to drug dose and retention interval.

Figure 1

Compartment placements throughout the experimental phases are represented with this schematic representation. Rats were conditioned and assigned to groups in an unbiased fashion. All compartment placements were counterbalanced according to rods/holes, spatial orientation, and whether drug and novelty pairings occurred on the first or second day if conditioning.

Figure 2

Mean time (± SEM) spent in seconds for rats in the Control and Novelty groups conditioned with 7.5, 20, and 30 mg/kg cocaine on the three tests of place conditioning in Experiment 1. Panel A shows data for rats conditioned with 7.5 mg/kg cocaine. Panel B represents data from the 20 mg/kg conditioning group and Panel C from the 30 mg/kg group. The Control group is represented in the left column and the Novelty group on the right. PC= place conditioning, DF= drug-free test, DC= drug challenge test. * Indicates significant difference between compartments.

Figure 3

Mean activity counts (± SEM) for rats conditioned with 7.5, 20, or 30 mg/kg cocaine in the Control and Novelty groups for Experiment 1. PC= place conditioning, DF= drug-free test, DC= drug challenge test. * Indicates significant difference on the drug challenge test in comparison to both other tests for rats in both groups.

Figure 4

Mean time (± SEM) spent in seconds in each compartment for rats conditioned with 10 mg/kg cocaine in the Control (left graph) and Novelty (right graph) conditions on the three tests of place conditioning in Experiment 2. PC= place conditioning, DF= drug-free test, DC= drug challenge test. * Significant difference between compartments.

Figure 5

Time spent (mean ± SEM) in each compartment for rats in the Control and Novelty groups for the three tests of place conditioning in Experiment 2. Drug-free testing occurred 14 and 28 days after conditioning and drug-challenge testing occurred 15 and 29 days after conditioning. Panel A depicts data from rats tested at 14 and 15 day retention intervals and Panel B shows the 28 and 29 day retention intervals. Control groups are in the left column and Novelty groups are in the right. PC= place conditioning, DF= drug-free test, DC= drug challenge test. * Indicates significant difference between compartments.

Figure 6

This figure shows activity scores (mean ± SEM) for rats tested at different retention intervals on the three tests of conditioning in Experiment 2. Figure 5a depicts the shortest retention interval in which drug-free and drug-challenge tests occurred 24 and 48 hrs, respectively, after the novelty-conditioning phase. Figure 5b shows activity scores for the longer retention intervals. Specifically, drug-free testing occurred 14 and 28 days after conditioning and drug-challenge testing occurred 15 and 29 days after conditioning. PC= place conditioning, DF= drug-free test, DC= drug challenge test. * Indicates significant difference on the drug challenge test in comparison to the drug-free test for both groups.