Delayed extinction and stronger reinstatement of cocaine conditioned place preference in adolescent rats, compared to adults

Abstract

Adolescence is a transitional period during development that is associated with a greater likelihood of addiction to drugs than any other age. One possibility for this observation is that learned associations between the rewarding experience of drugs and drug-related cues may produce greater motivational salience, and thus are more difficult to extinguish. Using an unbiased place-conditioning paradigm with two doses of cocaine (10 mg/kg or 20 mg/kg), the authors show here that adolescents require 75 +/- 17% more extinction trials than adults to extinguish cocaine place-preferences. Furthermore, once extinguished, adolescents display a greater preference for a previously cocaine-paired environment upon drug-primed reinstatement compared with adults. These results suggest that adolescent vulnerability to addiction involves robust memories for drug-associated cues that are difficult to extinguish. Therefore, drug-addicted adolescents may have a higher risk of relapse than adults, leading to greater prevalence of addiction in this population.

Figure 1

Adolescent rats require more extinction trials to extinguish conditioned place preferences for cocaine, compared to adults. Top and bottom graphs illustrate the acquisition and extinction of conditioned preference for an environment paired with 20 mg/kg cocaine (A) or 10 mg/kg cocaine (B). Numbers at each data point represent the number of animals that had not yet reached criterion and therefore remained in the experiment. Shaded boxes represent means ± SEM for adults that did not form preferences for the drug-paired environment, and therefore were excluded from further analyses. Preference scores represent the ratio of time spent in the drug-paired chamber to total time spent in both paired and unpaired chambers. Horizontal bars under each graph represent means ± SEM of the number of days required to reach extinction criterion for adolescent (filled) or adult (open) rats after conditioning to each dose of cocaine.

Figure 2

Reinstatement of conditioned place preference is achieved in adolescents conditioned to either 10 or 20 mg/kg cocaine, while reinstatement is achieved in adults only to environments paired with 20, but not 10 mg/kg cocaine. Bars represent means ± SEM of preference scores on the last extinction trial for each animal and after challenge with 5 mg/kg cocaine (24 hr after last extinction trial).