Hot Off the Press – July 7, 2021
Discriminative stimuli (DSs) play an important and understudied role in the persistent susceptibility to drug relapse. They signal drug availability (DS+) or unavailability (DS-) and control drug seeking prior to relapse. We previously demonstrated persistent DS-controlled cocaine seeking for up to 300 abstinence days in rats. In the current study, we examined the behavioral mechanisms and neurobiological substrates within prelimbic and infralimbic subregions of the medial prefrontal cortex (mPFC) that underly this persistent drug-seeking behavior. Our data indicates that during abstinence, DS+ and DS- independently control the expression and suppression of DS-controlled drug seeking, and that DS-controlled cocaine seeking (but not DS-guided discriminated cocaine seeking or DS-controlled cocaine self-administration) is mediated by infralimbic (but not prelimbic) cortex activity, likely via a presynaptic mechanism.