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

GUZMAN ANDREA SUSANA; AVALOS MARIA PAULA; EULIARTE PIA; SANCHEZ MARIANELA ADELA; RIGONI DAIANA; BOEZIO MARIA JULIETA; VIRGOLINI MIRIAM B; BOLLATI FLAVIA A.; CANCELA LILIANA M

Congreso; XXXV Congreso anual de la Sociedad Argentina de Investigación en Neurociencias.; 2020

Sociedad Argentina de Investigación en Neurociencias.

Previous findings from our lab have demonstrated pharmacologically the role of the cannabinoid CB1 receptors (CB1Rs) within nucleus accumbens core (NAcC) in restraint stress-induced reinstatement of extinguished cocaine-conditioned place preference (CPP). Given the well-established role of glutamatergic transmission within NAcC in reinstatement of cocaine seeking, we evaluated the effects of AM251, a highly selective CB1R antagonist, and ACEA, a highly selective agonist, on stress-induced changes in extracellular glutamate levels within NAcC under reinstatement conditions. In vivo microdialysis experiment in male Wistar rats, combined with HPLC and electrochemical detection was used. Firstly, a reinstating stress session (30 min of restraint), but not a non-reinstating stress session (15 min of restraint), increased the extracellular glutamate levels within NAcC in animals that were re-exposed to the drug-paired compartment after extinction of cocaine-CPP. Interestingly, the microinjection of AM251 directly into NAcC inhibited this stress-induced increase of glutamate, and the microinjection of ACEA potentiated it when combined with the non-reinstating stress. These data suggest that CB1Rs in NAcC modulate the context-specific enhancement of glutamate after restraint stress. These findings may be explained in the framework of a dysregulation of glutamate homeostasis in NAcC and provide neurochemical basis to investigate in vivo mechanisms underpinning stress-induced relapse.