Several evidences support the idea of a proactive influence of stress on drug-addiction.Studies from our laboratory revealed that repeated stress alters the capacityof a subsequent cocaine injection to modulate dendritic spine morphology, actindynamics and AMPAR expression in the nucleus accumbens (NA) core. We havedemonstrated that the inhibition of actinpolymerization in the NA prevents stress cross-sensitization with cocaine. Thus, the main goal of this project is to evaluate the impact of the actincytoskeleton in the changes underling thefacilitatory influence of cocaine after chronic stress. For this purpose wehave generated a lentivirus containing a short hairpin RNA (shRNA) specific to cofilin, to inhibit its expression in NA, and explore its function duringcross-sensitization between stress and cocaine. Thus, Wistar rats will be exposed to chronic restraintstress two hours daily during 7 days. Stressed and controlanimals will be administered with an intra-accumbens injection of lentiviralvector 20 days (day 8) before a challenge with cocaine administered 3 weeksafter the final stress (day 28), when behavioral sensitisation to cocaine wasevaluated. Our preliminarydata 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 pathwaysregulating cofilin activity during stress induced cross sensitization tococaine.