Inhibition of NFkB pathway in Nucleus Accumbens core prevents stress-induced cross-sensitization to cocaine

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

Córdoba

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

Sociedad Argentina de Investigación en Neurociencias

Inhibitionof NFkB pathway in Nucleus Accumbens core prevents stress-inducedcross-sensitization to cocaine Sanchez M.A.*, AvalosM.P.*, Guzman A.S, Boezio J., Rigoni D., Eluarte P.V., Bollati F., CancelaL.M. *equal contribution IFEC-CONICET, Departamento de Farmacología, Facultad deCiencias Químicas, Universidad Nacional de Córdoba. Stress isconsidered as one of the most significant risk factors to the development of substanceuse disorders. In animal models, stress can elicit a sensitized response to thepsychomotor and stimulating effects of cocaine. Our previous findings havepointed out that an enduring impairment of glutamate (GLU) homeostasis in theNucleus Accumbens (NAc) core underlies chronic restraint stress-induced cross-sensitizationto cocaine. The hallmark of this alteration was the increased basal levels of extracellular GLU and the blunted GLU levels in response tococaine within the NAc core inpre-stressed animals. Giventhat it has been reported a close linkage between GLU and the activation of Nuclear Factor-KappaB (NFκB), we posit that this stress-induced homeostatic disruptionof GLU underlying cross-sensitization to cocaine dependson NFκB signaling. This research attempts to study therole of accumbal NFκB pathway in the expression ofcocaine sensitization induced by chronic restraint stress. Thus, locomotoractivity was measured in response to a saline or cocaine injection inpre-stressed and non-stressed rats after a pre-treatment with an NFκB inhibitor (PDTC: 5, 10, 20 µM) or vehicle into the NAccore. Our results showed that the inhibition of NFκB pathway in the NAc coreprevents stress-induced cross-sensitization to cocaine in a dose-dependentmanner. This study deepensthe neurobiological mechanisms underpinning stress-induced cross-sensitizationto cocaine.