Role of cofilin in nucleus accumbens core during the cross-sensitization between chronic stress and cocaine

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

Mar del Plata- Buenos Aires

Congreso; XXX Congreso de la Sociedad Argentina de Investigación en Neurociencias.; 2015

Sociedad Argentina de Neurociencias

Several evidences support the idea of a proactive influence of stress on drug-addiction. Studies from our laboratory revealed that repeated stress alters the capacity of a subsequent cocaine injection to modulate dendritic spine morphology, actin dynamics and AMPAR expression in the nucleus accumbens (NA) core. We have demonstrated that the inhibition of actin polymerization in the NA prevents stress cross-sensitization with cocaine. Thus, the main goal of this project is to evaluate the impact of the actin cytoskeleton in the changes underling the facilitatory influence of cocaine after chronic stress. For this purpose we have generated a lentivirus containing a short hairpin RNA (shRNA) specific to cofilin, to inhibit its expression in NA, and explore its function during cross-sensitization between stress and cocaine. Thus, Wistar rats will be exposed to chronic restraint stress two hours daily during 7 days. Stressed and control animals will be administered with an intra-accumbens injection of lentiviral vector 20 days (day 8) before a challenge with cocaine administered 3 weeks after the final stress (day 28), when behavioral sensitisation to cocaine was evaluated. Our preliminary data suggests that the inhibition of cofilin is sufficient to prevent the expression of cross-sensitization between stress and cocaine. Future studies will attempt to identify the upstream signaling pathways regulating cofilin activity during stress induced cross sensitization to cocaine.