ABSTRACT
RATIONALE: 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. OBJECTIVES: 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 1 day after training (T1, early relapse) or following 15 days of abstinence (T15, late relapse). METHODS: Adolescent and adult rats received ABRV Coc-SA in a distinct context (2 hr, 2x/day over 5 days) then EXT in a second context (2 hr, 2x/day over 4 days). 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. RESULTS & CONCLUSIONS: 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.
Subject(s)
Cocaine-Related Disorders , Cocaine , Rats , Animals , Male , Rats, Sprague-Dawley , Pharmaceutical Preparations , Drug-Seeking Behavior , Self Administration , Cues , Recurrence , Extinction, Psychological , Conditioning, OperantABSTRACT
The authors have noted an error in Fig. 1B and Fig. 1C.
ABSTRACT
RATIONALE: 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. OBJECTIVES: 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. METHODS: 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. RESULTS AND CONCLUSIONS: 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.
