Endocannabinoidsystem, primarily through their actions at CB1 receptor (CB1R), is implicatedin drug relapse. Previous results from our lab demonstrated that in extinguishedcocaine-conditioned animals, evaluated in a conditioned place preference test(CPP), the administration of AM251, a CB1R antagonist, or ACEA, a CB1R agonist,into the Core of the Nucleus Accumbens (NAc) abrogated or facilitated restraintstress-induced reinstatement of cocaine-CPP responses, respectively. In orderto compare the involvement of both NAc compartments, extinguishedcocaine-conditioned Wistar rats were microinjected into the Shell of NAc with ACEA(0.01fmol/side), AM251 (10ug/side) or vehicle, and subsequently assigned to thefollowing treatments: 1) Stressed Animals (SA): 15 or 30 min-restraint exposure,depending on the experiment, and 2) Control Animals (CA). The intra-Shell administrationof CB1R antagonist or agonist did not modify the restraint stress-inducedreinstatement of cocaine-CPP responses as previously observed after intra-Coreadministration of CB1R ligands. These findings support the hypothesis of the preferentialinfluence of CB1R within NAc Core, but not Shell, in the reinstatement ofcocaine seeking behavior. Future studies will attempt to identify a possible glutamatedependent mechanism underpinning the effects of CB1R ligands on the restraintstress-induced reinstatement of cocaine-CPP responses.