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

SANCHEZ, M.A.; AVALOS, M.P.; GUZMAN, A.S.; BOEZIO M. JULIETA; RIGONI DAIANA; ELUARTE. P ; BOLLATI, FLAVIA A.; CANCELA LILIANA MARINA

Cordoba

Congreso; XXXIV Congreso de la sociedad Argentina de la investigacion en neurociencia; 2019

Sociedad Argentina de investigación en Neurociencia

Stress is considered as one of the most significant risk factors to the development of substance use disorders. In animal models, stress can elicit a sensitized response to the psychomotor and stimulating effects of cocaine. Our previous findings have pointed out that an enduring impairment of glutamate (GLU) homeostasis in the Nucleus Accumbens (NAc) core underlies chronic restraint stress-induced cross-sensitization to cocaine. The hallmark of this alteration was the increased basal levels of extracellular GLU and the blunted GLU levels in response to cocaine within the NAc core in pre-stressed animals. Given that it has been reported a close linkage between GLU and the activation of Nuclear Factor-Kappa B (NFκB), we posit that this stress-induced homeostatic disruption of GLU underlying cross-sensitization to cocaine depends on NFκB signaling. This research attempts to study the role of accumbal NFκB pathway in the expression of cocaine sensitization induced by chronic restraint stress. Thus, locomotor activity was measured in response to a saline or cocaine injection in pre-stressed and non-stressed rats after a pre-treatment with an NFκB inhibitor (PDTC: 5, 10, 20 µM) or vehicle into the NAc core. Our results showed that the inhibition of NFκB pathway in the NAc core prevents stress-induced cross-sensitization to cocaine in a dose-dependent manner. This study deepens the neurobiological mechanisms underpinning stress-induced cross-sensitization to cocaine.