Context-specific increase of extracellular glutamate in nucleus accumbens: a role in stress-induced reinstatement of cocaine-conditioned place preference.

GUZMAN, ANDREA S.; AVALOS, MARÍA P.; EULIARTE, PÍA V.; SANCHEZ, MARIANELA A.; RIGONI, DAIANA; BOLLATI, FLAVIA A.; VIRGOLINI, MIRIAM B.; CANCELA, LILIANA M.

Santiago de Compostela, Galicia, España

Congreso; 18th National Meeting of the Spanish Society of Neuroscience (SENC 2019); 2019

Spanish Society of Neuroscience

Exposure to a drug-paired context or stressors are considered the most important triggers that induce relapse in human addicts and in animal models of drug addiction, but the neurobiology of the interaction between these two factors to promote reinstatement has been scarcely studied. In this sense, pharmacological evidence from our lab support the critical role of the glutamatergic transmission within the nucleus accumbens (NAc) in stress-induced reinstatement of cocaine- conditioned place preference (CPP). The aim of the present study was to design a time course experiment in order to monitor in vivo transient changes in extracellular glutamate (GLU) levels within NAc in response to a re-exposure to the drug-paired compartment of the CPP apparatus after conditioning, extinction and stress-induced reinstatement of cocaine-CPP. In vivo microdialysis experiment in male Wistar rats, combined with high-performance liquid chromatography and electrochemical detection was used. On one hand, our results demonstrated that in vivo changes in extracellular GLU levels within NAc are related to the increased or the diminished preference for the drug-paired chamber after conditioning and extinction of cocaine-CPP, respectively. Moreover, results demonstrated the compartment-specific increase in extracellular levels of GLU within NAc in animals submitted to restraint stress after extinction of cocaine-CPP, since the ?unpaired group? and ?no stress group? did not show such GLU enhancement. The present study uniquely indicates that under the cocaine-CPP paradigm, it is plausible to demonstrate the concurrent context-dependent potentiation of behavioral and in vivo glutamatergic responses in absence of the drug occurring in conjunction with the restraint stress influence. This provides neurochemical basis to investigate mechanisms underpinning the influence of drug-related context in stress-induced reinstatement.