Context-drug-associations and reinstatement of drug-seeking behavior in male rats: Adolescent and adult time-dependent effects.

Abstract

Drug use during adolescence results in a life-long risk to develop substance-use disorders. Adolescent rats are sensitive to different drug-associated cues, compared to adults; however, the contribution of adolescent-formed context-drug-associations to elicit relapse-like behavior is underexplored. The present study compared the effect of adolescent vs adult-formed context-drug associations to elicit time-dependent increases in cocaine-seeking behavior. This objective was accomplished using an abbreviated (ABRV) operant cocaine self-administration (Coc-SA), Extinction (EXT) paradigm, with cocaine-seeking tests occurring 1day after training (T1, early relapse) or following 15days of abstinence (T15, late relapse). Adolescent and adult rats received ABRV Coc-SA in a distinct context (2 hr, 2x/day over 5days) then EXT in a second context (2 hr, 2x/day over 4days). Adolescent or adult cocaine-exposed rats were then tested (2 hr, non-rewarded) in either the previous EXT or Coc-paired contexts during early or late relapse. As previously reported, both adolescent and adult cocaine-exposed rats displayed similar magnitudes of cocaine intake and lever presses during Coc-SA, EXT, and early relapse. Independent analysis of adolescent and adult groups revealed differences in lever responding, specifically rats with cocaine exposure during adolescence showed time-dependent increases in lever responding during late relapse. These data suggest that cocaine-context associations formed during adolescence can elicit craving during adulthood and that these age-specific differences in contextual sensitivity may not be immediately observed at early relapse periods.