Combined Behavioral and Pharmacological Treatments to Prevent Common Mechanisms of Cocaine and Stress to trigger relapse to drug use.

CANCELA LM.; DE GIOVANNI L; AVALOS MP; GUZMAN A; MIRIAM VIRGOLINI; CANCELA LM.

Baltimore

Conferencia; Addiction Medicine and Reward Deficiency Syndrome; 2017

United Scientific Group

Relapse is a common feature of cocaine 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-induced relapse of drug-seeking behavior. There is evidence that the glutamate ionotropic NMDA and metabotropic mGluR2/3and mGluR5receptors are critically involved in drug- and cue-induced reinstatement of seeking behavior and drug-CPP responses. The aim of this study was to investigate the contribution of these receptors within nucleus accumbens (NAc) core vs. shell to restraint stress-induced reinstatement of cocaine-CPP. After extinction of cocaine-conditioned preference, animals were administered with the MK 801,MPEP or LY 379268, systemically and/or into intra-core or intra-shell before restraint (30 min) or left undisturbed in their home-cage. Three days later these animals were evaluated in a secondstress or drug-induced reinstatement. Since during the second reinstatementthe effect mirrored that observed in the first one, another set of experiments exploreda possible influence of the pharmacological treatments on the drug memory reconsolidation processes. First, we demonstrated that restraint stress-induced reinstatement of extinguished cocaine-CPP was blocked by MK 801or MPEPintra-core, but not intra-shell,administration. Second, we showed that all pharmacological treatments administered immediately, but not three hours later,ofthe first stress-induced reinstatement or the reactivation/evocation session (without stress exposure) suppressed a second stress or drug-induced relapse to cocaine. Pharmacological treatments during the memory reconsolidation window could help to prevent relapse to drug use following stress or drug.