Severalevidences support the idea of a proactive influence of stress ondrug-addiction. Studies from our laboratory revealed that repeated stress altersthe capacity of a subsequent cocaine injection to modulate dendritic spinemorphology, actin dynamics and AMPAR expression in the nucleus accumbens (NA)core. We have demonstrated that the inhibition actin polymerization in theNA prevents stress cross-sensitization with cocaine. Thus, the main goal ofthis project is to evaluate the impact of the actin cytoskeleton in the changesunderling the facilitatory influence of cocaine after chronic stress. For thispurpose we have generated a lentivirus containing a short hairpin RNA (shRNA)specific to cofilin, to inhibit its expression in NA, and explore its functionduring cross-sensitization between stress and cocaine. Thus, Wistar rats willbe exposed to chronic restraint stress two hours daily during 7 days. Stressedand control animals will be administered with an intra-accumbens injection oflentiviral vector 20 days (day 8) before a challenge with cocaine administered3 weeks after the final stress (day 28), when behavioral sensitisation to cocainewas evaluated. Our preliminary data suggests that the inhibition of cofilin issufficient to prevent the expression of cross-sensitization between stress andcocaine. Future studies will attempt to identify the upstream signalingpathways regulating cofilin activity during stress induced cross sensitizationto cocaine.