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

EULIARTE PIA V; RIGONI D; AVALOS M.P; BOEZIO M.J; CANCELA L.M; GUZMAN A.S; SANCHEZ M.A; BOLLATI F

Cordoba

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

Sociedad Argentina de Investigación en Neurociencias

CB1 receptor agonism potentiated stress-inducedenhancement of extracellular glutamate in nucleus accumbens core afterextinction of cocaine-conditioned place preference.Guzman, Andrea S.; Avalos, María P.; Euliarte, PiaV.; Sanchez, Marianela A.; Rigoni, Daiana; Boezio, Julieta; Bollati, Flavia A.;Cancela, Liliana M.IFEC-CONICET, Departamento de Farmacología, Facultad de CienciasQuímicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaStress is considered animportant factor that induces relapse in human addicts and in animal models ofaddiction. Findings from our lab have demonstrated pharmacologically the roleof the cannabinoid CB1 receptors within Core, but not Shell, subregion ofnucleus accumbens (NAc) in restraint stress-induced reinstatement ofextinguished cocaine- conditioned place preference (CPP). Specifically,activation of CB1 receptors with ACEA, a highly selective agonist, inducedreinstatement of cocaine-CPP when was administered directly into NAc Corebefore a non-reinstating session of stress (15 min of restraint). Given thewell-established role of glutamatergic transmission within NAc Core inreinstatement of cocaine seeking, we evaluated the effects of ACEA, onstress-induced changes in extracellular glutamate levels within NAc Core underreinstatement conditions. In vivo microdialysis experiment in male Wistar rats,combined with high-performance liquid chromatography and electrochemicaldetection was used. Firstly, our results demonstrated that a reinstating stresssession (30 min of restraint), but not a non-reinstating stress session (15 minof restraint), induced an increase in extracellular glutamate levels within NAcCore in animals that were re-exposed to the drug-paired compartment afterextinction of cocaine-CPP. Interestingly, we found that the microinjection ofACEA (20pM) directly into NAc Core in combination with the non-reinstatingstress session induced such increase in extracellular glutamate levels withinNAc Core. These data suggest that accumbal microinjection of ACEA mightfacilitate stress-triggered reinstatement of cocaine-CPP by potentiating thecontext-specific enhancement of NAc glutamate after a subthreshold session of restraintstress. This study provides neurochemical basis to investigate the in vivo mechanismsunderpinning the involvement of CB1 receptors within NAc Core in stress-inducedreinstatement.