CB1 receptor agonism potentiated stress-induced enhancement of extracellular glutamate in nucleus accumbens core after extinction of cocaine-conditioned place preference

EULIARTE, PIA VALENTINA; RIGONI, DAIANA; AVALOS, MARÍA P.; BOEZIO, JULIETA; CANCELA, LILIANA M.; GUZMÁN, ANDREA S.; SANCHEZ, MARIANELA ADELA; BOLLATI, FLAVIA A.

Carlos Paz, Cordoba

Congreso; XXXIV Congreso de la Sociedad Argentina de Investigación en Neurociencias; 2019

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). Specifically, activation of CB1 receptors with ACEA, a highly selective agonist, induced reinstatement of cocaine-CPP when was administered directly into NAc Core before anon-reinstating session of stress (15 min of restraint). Given the well-established role of glutamatergic transmission within NAc Core in reinstatement of cocaine seeking, we evaluated the effects of ACEA, on stress-induced changes in extracellular glutamate levels within NAcCore 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),but not a non-reinstating stress session (15 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. Interestingly, we found that the microinjection of ACEA (20pM) directly into NAc Core in combination with the non-reinstating stress session induced such increase in extracellular glutamate levels within NAc Core. These data suggest that accumbal microinjection of ACEA might facilitate stress-triggered reinstatement of cocaine-CPP by potentiating the context-specific enhancement of NAc glutamate after a subthreshold session of 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.