Distinct, learning-dependent neural mechanisms regulating cocaine and heroin seeking

Considerable evidence from rodent self-administration experiments implicates the infralimbic cortex (IL) and insular cortex (IC) in suppressing and promoting cocaine seeking, respectively. However, it is unclear whether these regions similarly regulate opioid seeking. Moreover, the degree to which these neural mechanisms depend on learned action-outcome contingencies is uncertain. The present experiments used optogenetic and pharmacological manipulations, in female and male rats that had learned to press a lever to self-administer heroin, to investigate the role of the IL and IC in heroin extinction learning and cued heroin seeking, respectively. Additionally, we developed a novel discriminative stimulus-based task for cocaine self-administration with directly competing contingencies.