CB1R activation in nucleus accumbens core promotes stress-induced reinstatement of cocaine seeking by elevating extracellular glutamate in a drug-paired context

GUZMAN, ANDREA S.; AVALOS, MARIA P.; DE GIOVANNI, LAURA N.; EULIARTE, PIA V.; SANCHEZ, MARIANELA A.; MONGI-BRAGATO, BETHANIA; RIGONI, DAIANA; BOLLATI, FLAVIA A.; VIRGOLINI, MIRIAM B.; CANCELA, LILIANA M.

Scientific Reports

Nature Research

Año: 2021 vol. 11

reclinical models of stress-induced relapse to drug use have shown that the dysregulation of glutamatergic transmission within the nucleus accumbens (NA) contributes notably to the reinstatement of cocaine-seeking behavior in rodents. In this sense, there has been increasing interest in the cannabinoid type-1 receptor (CB1R), due to its crucial role in modulating glutamatergic neurotransmission within brain areas involved in drug-related behaviors. This study explored the involvement of CB1R within the NA subregions in the restraint stress-induced reinstatement of cocaine-conditioned place preference (CPP), as well as in the regulation of glutamatergic transmission, by using a pharmacological approach and the in vivo microdialysis sampling technique in freely moving rats. CB1R blockade by the antagonist/inverse agonist AM251 (5 nmol/0.5 μl/side) or CB1R activation by the agonist ACEA (0.01 fmol/0.5 μl/side), prevented or potentiated restraint stress-induced reinstatement of