CB1 receptor antagonism inhibits stress-induced enhancement of extracellular glutamate in nucleus accumbens core after extinction 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.

Chicago, Illinois

Congreso; 2019 Neuroscience Meeting.; 2019

Society for Neuroscience

Stress is considered an important factor that induces relapse in human addicts and in animal models of addiction. Findings from our lab have demonstrated pharmacologically the role of the cannabinoid CB1 receptors within Core, but not Shell, subregion of nucleus accumbens (NAc) in restraint stress-induced reinstatement of extinguished cocaine- conditioned place preference (CPP). Given the well-established role of glutamatergic transmission within NAc Core in reinstatement of cocaine seeking, we evaluated the effects of AM251, a highly selective CB1 receptor antagonist, on stress-induced changes in extracellular glutamate levels within NAc Core under reinstatement conditions. In vivo microdialysis experiment in male Wistar rats, combined with high-performance liquid chromatography and electrochemical detection was used. Firstly, our results demonstrated that a reinstating stress session (30 min of restraint) induced an increase in extracellular glutamate levels within NAc Core in animals that were re-exposed to the drug-paired compartment after extinction of cocaine-CPP, while the ?unpaired group? and ?no stress group? of animals did not show such glutamate enhancement. Moreover, we found that microinjection of AM251 (10 ug/ul) directly into NAc Core, inhibited the observed stress-induced increase of glutamate in the same area. These data suggest that accumbal microinjection of AM251 prevents stress-triggered reinstatement of cocaine-CPP by inhibiting the context-specific enhancement of NAc glutamate after restraint stress. This study provides neurochemical basis to investigate the in vivo mechanisms underpinning the involvement of CB1 receptors within NAc Core in stress-induced reinstatement.