The health and economic costs associated with substance use disorders (SUDs) are immense, with a rise in overdose deaths related to stimulant or stimulant and opiate use from 2016-2021 (NIDA). Drug use during adolescence increases the risk for development of SUDs, with the severity of diagnosis associated with worse outcomes later in life. Recent reports of increased stimulant use among 15–23-year-olds and the number of overdose deaths associated with cocaine use highlight the need to understand both the behavioral and underlying molecular changes associated with craving and relapse in this age group.We developed an abbreviated cocaine self-administration (Coc-SA) procedure which allowed us to examine relapse during adolescence and found that the magnitude of contextual cocaine-seeking is the same for adolescent and adult cocaine-exposed rats after 1 day of abstinence. However, adolescent rats had significantly higher seeking after 15 days of abstinence (incubation of craving). The current proposal aims to examine whether changes in plasticity, specifically activation of NMDA and AMPA receptor subunits, occur during abstinence periods that precede relapse. Adolescent and adult rats received Coc-SA in a distinct context (2h sessions, 2x/day, minimum 10 sessions), followed by extinction training (EXT) in a second distinct context (2h session, 2x/day, minimum 8 session). Adolescent and adult rats were split into three separate Relapse Test groups: No Test (30min in homecage), Test in the EXT context (EXT), Test in the Cocaine-paired context after 1 day (T1), or 15 days (T15) of abstinence. Tissue samples from the dorsal hippocampus were collected 30min after Relapse Tests. We found increased cocaine-seeking behavior in adolescent and adult rats after 15 days of abstinence, however we did not observe Age or Relapse Test-dependent changes in NMDA or AMPA subunit activation associated with craving and relapse.
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