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

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

Paris

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

Differential role of CB1 receptors within accumbalsubregions in stress-induced reinstatement of cocaine?conditioned preferenceGUZMAN, A.S.; DE GIOVANNI,L.N.; VIRGOLINI, M.B.; CANCELA, L.M.IFEC-CONICET. Departamento de Farmacología. FCQ. UNCStress is consideredone of the most important factors known that induces relapse in human addictsand in animal models of drug addiction. Research from our laboratorydemonstrates that, using a conditioned place preference (CPP) paradigm, anacute restraint stress exposure triggers reinstatement of cocaine-CPP. Withregard to the neurobiological mechanisms underlying relapse, there are numerousevidences for the participation of the endocannabinoid system (ECS), primarilythrough their actions at the widely distributed CB1 receptors (CB1R).Nevertheless, the role of ECS in stress-induced reinstatement has not beenextensively studied. Considering that subregions of the Nucleus Accumbens (NAc)contribute significantly, but differently, to the impact of drug and stress onaddiction, the present study has been designed to evaluate the involvement ofCB1R within Core and Shell compartments of NAc in a restraint stress?inducedreinstatement model. Male Wistar rats (220-300g) that extinguished cocaine-CPP weremicroinjected 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), subsequentlyassigned to the different treatments of restraint stress exposure and thentested for reinstatement of cocaine-CPP. Results show that the intra-Core administrationof AM251 abrogated restraint stress-induced reinstatement, and ACEA facilitatedreinstatement after a non-reinstatement stress exposure (15 min). Moreover, thefacilitating effect of ACEA was prevented by pretreatment with a microinjectionof AM251. Interestingly, these effects were not observed after CB1R ligandsmicroinjection into the NAc Shell compartment. Our results support thehypothesis of the preferential influence of CB1R within NAc Core, but notShell, in the reinstatement of cocaine seeking behavior. This conclusion is inaccordance with previous results of our lab that demonstrate the preferentialrole of glutamatergic transmission within NAc Core in the same model. Futuresstudies will attempt to confirm a possible glutamate dependent mechanismunderpinning the effects of CB1R ligands on the restraint stress-inducedreinstatement of cocaine-CPP responses.