Participation of cofilin in the sensitization between chronic stress and cocaine in nucleus accumbens core

RIGONI DAIANA; AVALOS, M.P.; BISBAL MARIANO; BOEZIO M. JULIETA; CANCELA L.M; BOLLATI FLAVIA

Córdoba

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

Sociedad Argentina de Investigación en Neurociencias

It has been demonstrated that exposure to stress predisposes to developing substance use disorders. Our previous results have shown long-term changes in proteins that regulate actin cytoskeleton in the nucleus accumbens core (NAc) during the expression of cross-sensitization between stress and cocaine. We described modifications in levels of cofilin phosphorylation along with an increase in the PSD size and an enhancement in AMPAR surface expression in NAc. Here, we evaluate the influence of cofilin, a direct regulator of actin cytoskeleton remodeling, during stress-induced sensitization to cocaine. For this purpose, we have generated a lentivirus containing an interference RNA specific to suppress cofilin expression (shRNAcofilin) and explore its function and changes associated with long-term plasticity in NAc. Thus, chronically pre-stressed male rats were administered intra-NAc with shRNAcofilin, 20 days before a challenge with cocaine, when behavioral sensitization was evaluated. Additionally, we examined changes in the AMPAR surface expression and spine morphology, thought to contribute to the expression of cocaine sensitization. Our findings reveal that the inhibition of cofilin, is sufficient to prevent stress-induced sensitization to cocaine and impedes the GluR1 surface enhancement in NAc, in pre-stressed animals. These findings constitute a molecular mechanism influencing actin cytoskeleton remodeling in the NAc during cross sensitization between stress and cocaine.