Cocaine-use disorders are characterized by repeated relapse to drug-seeking and drug-taking behavior following periods of abstinence. Former drug users display increased activation of the orbitofrontal cortex (OFC) in response to drug-related cues, and similar phenomena are also observed in rodent models of drug relapse. The lateral, but not medial, OFC functionally contributes to the maintenance of cue-drug associations; however, less is known about the role of the ventral OFC in this process. To examine the pattern of neuronal activation in OFC subregions in response to drug-associated cues, rats were trained to respond on a lever for a cocaine infusion paired with a complex cue (2-hr sessions, minimum 10 days). Cocaine self-administration was followed by extinction training, in which lever responses resulted in no consequences (2-hr sessions, minimum 7 days). During a 1-hr reinstatement test, drug-seeking behavior (i.e., responses on the drug-paired lever) was examined in the presence or absence of contingent drug-paired cues (Cue TEST vs. Ext TEST, respectively). Rats were overdosed with a ketamine + xylazine cocktail 30-min post session, and transcardially perfused with 4% paraformaldehyde. Cfos protein expression was utilized to measure potential changes in neural activation between the reinstatement test groups. An increase in the number of Cfos-Immunoreactive cells was observed in the ventral and lateral subregions of the OFC in the Cue TEST group. The present findings provide evidence that the ventral and lateral regions of the rat OFC display similar patterns of neuronal activation in response to cocaine-paired cues.

Rationale: Drug use during adolescence results in a life-long risk to develop substance-use disorders. Adolescent rats are less reactive to cocaine-associated cues compared to 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 is unknown.Objectives: The present study compared the effect of adolescent vs adult-formed context-drug associations under differential 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 hr, 1x/day, 10 days), extinction training (EXT) in a second context (1 hr, 1x/day, 8 days) with reinstatement test (TEST) during adulthood in the cocaine-paired context. In experiments 2-3, rats received all behavioral phases during adolescence or adulthood: ABRV Coc-SA (2 hr, 2x/day, 5 days), EXT (1 hr, 4x/day, 2 days) with TEST in a cocaine-paired or novel, unpaired context. All experiments included pair and single-housing conditions.Results & 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.

No abstract

No abstract