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

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

Cordoba

Congreso; XXXIV Congress of the Argentine Society for Research in Neuroscience; 2019

Sociedad Argentina de Investigacion en Neurociencias

Participation of cofilin in the sensitization between chronic stress andcocaine in nucleus accumbens core.Daiana Rigoni 1, Maria P. Avalos 1, Mariano Bisbal 2,M. Julieta Boezio1, Andrea S. Guzman 1, Liliana M.Cancela 1, Flavia Bollati 1 (1)IFEC- CONICET. Departamento deFarmacología, Fac. De Ciencias Químicas, Universidad Nacional de Córdoba,Argentina.(2)Instituto Ferreyra(INIMEC-CONICET-Universidad Nacional de Córdoba), Córdoba, Argentina. Ithas been demonstrated that exposure to stress predisposes todeveloping substance use disorders. Our previous results have shown long-termchanges in proteins that regulate actin cytoskeleton in the nucleus accumbenscore (NAc) during the expression of cross-sensitization between stress andcocaine. We described modifications in levelsof cofilin phosphorylation along with an increase in the PSD size and anenhancement in AMPAR surface expression in NAc. Here, we evaluate the influenceof cofilin, a direct regulator of actin cytoskeleton remodeling, during stress-inducedsensitization to cocaine. For this purpose, we have generated a lentiviruscontaining 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 withshRNAcofilin, 20 days before a challenge with cocaine, when behavioralsensitization was evaluated. Additionally, we examined changes in the AMPARsurface expression and spine morphology, thought to contribute to theexpression of cocaine sensitization. Our findings reveal that the inhibition ofcofilin, is sufficient to prevent stress-induced sensitization to cocaine and impedesthe GluR1 surface enhancement in NAc, in pre-stressed animals. These findingsconstitute a molecular mechanism influencing actin cytoskeleton remodeling inthe NAc during cross sensitization between stress and cocaine.This work wassupported by grants from ISN, CONICET, SECYT and FONCYT.