Differential rol of CB1 receptors within accumbal subregions in stress-induced reinstatment of cocaine-conditioned preference

GUZMAN A.S; LAURA DE GIOVANNI; VIRGOLINI, M.B; CANCELA L.M

Paris

Congreso; 2017 Meeting of the International Society for Neurochemistry and the European Society for Neurochemistry; 2017

Stress is considered one of the most important factors known that induces relapse in human addicts and in animal models of drug addiction. Research from our laboratory demonstrates that, using a conditioned place preference (CPP) paradigm, an acute restraint stress exposure triggers reinstatement of cocaine-CPP. With regard to the neurobiological mechanisms underlying relapse, there are numerous evidences for the participation of the endocannabinoid system (ECS), primarily through their actions at the widely distributed CB1 receptors (CB1R). Nevertheless, the role of ECS in stress-induced reinstatement has not been extensively studied. Considering that subregions of the Nucleus Accumbens (NAc) contribute significantly, but differently, to the impact of drug and stress on addiction, the present study has been designed to evaluate the involvement of CB1R within Core and Shell compartments of NAc in a restraint stress?induced reinstatement model. Male Wistar rats (220-300g) that extinguished cocaine-CPP were microinjected into the Core or into the Shell of NAc with a CB1R agonist (ACEA; 0.001 or 0.01fmol/side) or a CB1R antagonist (AM251; 5 or 10ug/side), subsequently assigned to the different treatments of restraint stress exposure and then tested for reinstatement of cocaine-CPP. Results show that the intra-Core administration of AM251 abrogated restraint stress-induced reinstatement, and ACEA facilitated reinstatement after a non-reinstatement stress exposure (15 min). Moreover, the facilitating effect of ACEA was prevented by pretreatment with a microinjection of AM251. Interestingly, these effects were not observed after CB1R ligands microinjection into the NAc Shell compartment. Our results support the hypothesis of the preferential influence of CB1R within NAc Core, but not Shell, in the reinstatement of cocaine seeking behavior. This conclusion is in accordance with previous results of our lab that demonstrate the preferential role of glutamatergic transmission within NAc Core in the same model. Futures studies will attempt to confirm a possible glutamate dependent mechanism underpinning the effects of CB1R ligands on the restraint stress-induced reinstatement of cocaine-CPP responses.