Medial prefrontal cortical neurotransmitters reactive to relapse-promoting and relapse-suppressing cues in rats trained to self-administer cocaine or alcohol

Abstract

Environmental cues conditioned to signal drug availability (S+) or omission (S-) activate specific neurons (neuronal ensembles/engram cells) within the medial prefrontal cortex (mPFC) to promote and suppress drug relapse in rats. However, the neurochemical source of such cue-specific activation remains unknown. In this study, we determined extracellular neurotransmitter fluctuations reactive to S+ vs. S- in the infralimbic (IL) and prelimbic (PL) cortices of male rats trained to lever-press for cocaine or alcohol self-administration. In cocaine- or alcohol-trained rats exposed to S+, no significant neurotransmitter fluctuations were observed in IL or PL. In cocaine-trained rats exposed to S-, glutamate, serotonin, taurine and adenosine were increased in PL but not in IL. In alcohol-trained rats exposed to S-, glutamate was increased, while dopamine and GABA were decreased, in IL but not in PL. Although S+ reactive neurotransmitters driving neuronal activation in mPFC remains to be elucidated, glutamate is likely the source of such activation by S- in rats trained to self-administer cocaine or alcohol. While drugs used for self-administration and cue-conditioning appear to dictate the type and anatomical specificity of S- evoked neurotransmission within mPFC, glutamate may serve as a common therapeutic target to mimic relapse-suppression by S- across cocaine and alcohol use disorders (CUD and AUD). In contrast, serotonin, taurine and adenosine may serve as the targets in CUD, while dopamine and GABA may serve as the targets in AUD.