CONICET | Buscador de Institutos y Recursos Humanos

It is well known that there is a high rate of co-occurrence of substance abuse disorders andstressful life experiences. It has been shown that both drug administration and exposure tostress induce adaptations at the level of synapses involving modifications in the density andmorphology of dendritic spines that are regulated, at least in part, by a small GTPase knownas Rac1. Evidence from our laboratory revealed that repeated stress alters the capacity of asubsequent cocaine injection to modulate dendritic spine morphology and actin dynamics inthe NA core. Moreover, the pharmacological inhibition of actin polymerization in the NAprevents stress cross-sensitization with cocaine. Thus, the main goal of this project is toevaluate whether changes in Rac1 signaling induced by chronic stress, facilitate thedevelopment of sensitization to cocaine. For this purpose, we have generated lentiviralparticles containing a constitutive active form of Rac1 (CA-Rac1) to express in NA, andexplore its function during cross-sensitization between stress and cocaine. Thus, Wistar ratswill be exposed to chronic restraint stress two hours daily during 7 days. Stressed and controlanimals will be administered with an intra-accumbens injection of CA-Rac1 before achallenge with cocaine, when behavioral sensitization will be evaluated. Our data suggeststhat the expression of the active form of Rac1 is sufficient to prevent the expression of crosssensitizationbetween stress and cocaine.