Relapse is a common feature ofcocaine addiction. In rodents, it can be elicited by cues, stress or the drug.Restraint stress-induced reinstatement of cocaine-conditioned place preference(CPP) is a useful model to study the mechanisms involved in stress-inducedrelapse of drug-seeking behavior. There is evidence that the glutamate ionotropicNMDA and metabotropic mGluR2/3 and mGluR5 receptors are critically involved indrug- and cue-induced reinstatement of seeking behavior and drug-CPP responses.The aim of this study was to investigate the contribution of these receptorswithin nucleus accumbens (NAc) core vs. shell to restraint stress-induced reinstatement ofcocaine-CPP. After extinction of cocaine-conditioned preference, animals wereadministered with the MK 801, MPEP or LY 379268, systemically and/or intointra-core or intra-shell before restraint (30 min) or left undisturbed intheir home-cage. Three days later these animals were evaluated in a second stressor drug-induced reinstatement. Since during the second reinstatement the effectmirrored that observed in the first one, another set of experiments explored apossible influence of the pharmacological treatments on the drug memory reconsolidationprocesses. First, we demonstrated that restraint stress-induced reinstatementof extinguished cocaine-CPP was blocked by MK 801 or MPEP intra-core,but not intra-shell, administration. Second, we showed that all pharmacologicaltreatments administered immediately, but not three hours later, of the first stress-inducedreinstatement or the reactivation/evocation session (without stress exposure)suppressed a second stress or drug-induced relapse to cocaine. Pharmacologicaltreatments during the memory reconsolidation window could help to preventrelapse to drug use following stress or drug.