INVOLVEMENT OF CANNABINOID CB1 RECEPTORS WITHIN NUCLEUS ACCUMBENS CORE BUT NOT SHELL IN STRESS-INDUCED REINSTATEMENT IN EXTINGUISHED COCAINE?CONDITIONED ANIMALS

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

Valparaíso

Simposio; International Symposium NuMIND "Biology of Neuropsychiatric Disorders".; 2016

Millennium Nucleus Biology of Neuropsychiatric Disorders (NuMIND)

Relapse to drug abuse is a common feature of drug addiction. Stress is considered an important factor that induces relapse in human and can be modeled in laboratory animals. Previous results in our lab have demonstrated that in animals evaluated in a conditioned place preference (CPP) paradigm, an acute restraint stress exposure triggers reinstatement of cocaine-CPP. In respect to the neurotransmission systems involved in these behaviors, there are evidences related to the participation of endocannabinoid system, primarily through their actions at CB1 receptors (CB1R), in relapse to drug seeking. Moreover, several studies suggested that Nucleus Accumbens (NAc) is one of the main mesocorticolimbic brain region involved in the drug and stress impact on addiction. The present study has been designed to evaluate the involvement of CB1R within both compartments of NAc, Core and Shell, in 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), a CB1R antagonist (AM251; 5 or 10ug/side) or vehicle, subsequently assigned to the following treatments and then tested in the CPP apparatus: 1) Stressed Animals (SA): 15 or 30 min-restraint exposure, depending on the experiment, and 2) Control Animals (CA). 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). Interestingly, these effects of CB1R ligands after intra-Core administration were not observed after CB1R ligands microinjection into the 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