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

CANCELA, LM; DE GIOVANNI; AVALOS MP; GUZMAN AS; VIRGOLINI MB; BOLLATI FA

Baltimore

Conferencia; 2nd International Conference on 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 modelto study the mechanisms involved in stress-induced relapse of drug-seeking behavior. There is evidencethat the glutamate NMDA receptors are critically involved in drug- and cue-induced reinstatement ofseeking behavior and drug-CPP responses. The aim of this study was to investigate the contribution ofNMDA receptors within core vs. shell nucleus accumbens (NAc) subregions to restraint stress-inducedreinstatement of extinguished cocaine-CPP. After extinction of cocaine-conditioned preference, animalswere administered MK 801 systemically or directly into intra-core or intra-shell, and restrained for 30 minor left undisturbed in their home-cages. First, we demonstrated that restraint stress-induced reinstatementof extinguished cocaine-CPP depends on the duration of restraint as well as on the context in whichit is applied. Second, this effect was blocked by systemic MK 801 administration either before or afterrestraint. Third, intra-core but not intra-shell administration abrogated the restraint stress-induced reinstatement.These findings show that NMDA receptors within NAc core, but not shell, play a critical rolein restraint stress-induced reinstatement of cocaine-CPP.