Role of adolescent-formed, context-drug-associations on reinstatement of drug-seeking behavior in rats.

Drug use during adolescence results in a lifelong risk to develop substance-use disorders. Adolescent rats are less reactive to cocaine-associated cues compared with adults; however, the contribution of adolescent-formed, context-drug-associations to elicit relapse-like behavior is underexplored. Although it is known that social isolation can impact drug-seeking behavior, the effects of housing conditions on context-induced, cocaine-seeking during adolescence vs adulthood are unknown. The present study compared the effect of adolescent vs adult-formed context-drug associations under different housing conditions (pair vs single) on cocaine-seeking behavior during adolescence or adulthood. This objective was accomplished using operant cocaine self-administration (Coc-SA) under a standard, non-abbreviated (Non-ABRV) or modified abbreviated (ABRV) paradigm. In experiment 1, adolescent and adult rats received Non-ABRV Coc-SA in a distinct context (2 h, 1×/day, 10 days), and extinction training (EXT) in a second context (1 h, 1×/day, 8 days) with reinstatement test (TEST) during adulthood in the cocaine-paired context. In experiments 2 and 3, rats received all behavioral phases during adolescence or adulthood: ABRV Coc-SA (2 h, 2×/day, 5 days), EXT (1 h, 4×/day, 2 days) with TEST in a cocaine-paired or novel, unpaired context. All experiments included pair and single-housing conditions. Age at cocaine exposure did not influence behavior in Non-ABRV or ABRV paradigms. Under Non-ABRV conditions, adolescent and adult single-housed rats had higher seeking behavior than pair housed. These data suggest that social isolation influences context-induced, cocaine-seeking regardless of age at drug exposure and provides a condensed, ABRV paradigm to investigate context-induced, cocaine-seeking behavior during adolescence.