Essential role for Rac1 in chronic stress- induced sensitization to cocaine in nucleus accumbens.

RIGONI, D.; BOEZIO, MARÍA J.; AVALOS, M. P.; GUZMÁN, A. S.; SANCHEZ, M. A.; BISBAL, M.; CANCELA, L.M; BOLLATI, F.

Virtual

Congreso; XXXV Reunion Anual de la Sociedad Argentina de Investigacion en Neurosciencias; 2020

Sociedad Argentina de Investigacion en Neurosciencias

Several laboratories have demonstratedthat the RhoGTPaseRac1 mediates structural and behavioral plasticity inresponse to cocaine exposure in nucleus accumbens(NA). Specifically, repeatedexposure to cocaine negatively regulates Rac1 activity in NA and is responsibleforthe expansion of dendritic spines, through a mechanism mediated by Cofilin.Our previous results haveshown long-term changes in proteins regulatingactin cytoskeleton in the NA during the expression of cross-sensitizationbetween stress and cocaine. We havepreviously described modifications in levels of Cofilinphosphorylation andenhancement in AMPAR surface expression in NA core. Thus, the maingoal of thisproject is to evaluate the role of Rac1 signaling pathway in thedevelopment of cocaine sensitization induced bystress. For thispurpose, we have generated a lentivirus overexpressing Rac1 protein or a shRNA tosuppressCofilin expression, that were administered intra-NA core before achallenge with cocaine in pre-stressedrats, when behavioral sensitization wasevaluated. Additionally, we have examined changes in the AMPARsurfaceexpression. Our findings reveal that the overexpression of Rac1 is sufficientto prevent stress-inducedsensitization to cocaine and impedes the GluR1surface enhancement in NA core observed in pre-stressedanimals. These findingsconstitute a molecular mechanism influencing actin cytoskeleton remodeling intheNA during cross sensitization between stress and cocaine.