SAN2020

Previous findings from our lab have demonstrated pharmacologically the role of the cannabinoid CB1 receptors (CB1Rs) within nucleus accumbens core (NAcC) in restraint stress-induced reinstatement of extinguished cocaine-conditioned place preference (CPP). Given the well-established role of glutamatergic transmission within NAcC in reinstatement of cocaine seeking, we evaluated the effects of AM251, a highly selective CB1R antagonist, and ACEA, a highly selective agonist, on stress-induced changes in extracellular glutamate levels within NAcC under reinstatement conditions. In vivo microdialysis experiment in male Wistar rats, combined with HPLC and electrochemical detection was used. Firstly, a reinstating stress session (30 min of restraint), but not a non-reinstating stress session (15 min of restraint), increased the extracellular glutamate levels within NAcC in animals that were re-exposed to the drug-paired compartment after extinction of cocaine-CPP. Interestingly, the microinjection of AM251 directly into NAcC inhibited this stress-induced increase of glutamate, and the microinjection of ACEA potentiated it when combined with the non-reinstating stress. These data suggest that CB1Rs in NAcC modulate the context-specific enhancement of glutamate after restraint stress. These findings may be explained in the framework of a dysregulation of glutamate homeostasis in NAcC and provide neurochemical basis to investigate in vivo mechanisms underpinning stress-induced relapse.