Differential effects of self-administered cocaine in adolescent and adult rats on stimulus–reward learning

Abstract

Adult cocaine addicts, abstinent at the time of testing, show a variety of neurocognitive impairments. Less clear is whether there are differences in the degree of impairment if cocaine use is initiated during adolescence rather than adulthood. Using a preclinical model, we evaluated if stimulus-reward learning was impacted differently in rats exposed to cocaine during adolescence (beginning on postnatal day 37) vs adulthood (beginning on postnatal days 74-79) and then tested after a drug-free period. A yoked-triad design of intravenous cocaine self-administration in adult (n = 8 triads) and adolescent (n = 8 triads) rats was used. Sets of three animals either contingently self-administered cocaine or received cocaine or saline in a noncontingent manner. Rats self-administering 1-mg/kg doses of cocaine responded under a fixed-ratio 5, timeout 20-s schedule of reinforcement. After 18 2-h drug or saline sessions, all rats (now adults) began the drug-free period in their home environments. Testing in a stimulus-reward learning task (conditioned cue preference) began 19 days later. Self-administration behavior was similar in adolescent and adult rats. Lever responses were not significantly different, and both age groups averaged approximately 20 infusions per session. Rats contingently self-administering cocaine or passively exposed to cocaine during adulthood showed stimulus-reward learning deficits in the conditioned cue preference task. Rats exposed to contingent or noncontingent cocaine during adolescence had normal learning, showing strong preferences for a Froot Loops-paired cue. These findings suggest that adolescents are insensitive to cocaine-induced impairment of learning related to amygdala memory system functioning.