CONICET | Buscador de Institutos y Recursos Humanos

Rac1 isessential for the expression of behavioral sensitization induced by chronicstress in nucleus accumbensDaiana Rigoni 1, Maria P. Avalos 1, Mariano Bisbal 2,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 deInvestigación Médica M. y M. Ferreyra, Córdoba, Argentina. It is well known that there is ahigh rate of co-occurrence of substance abuse disorders and stressful lifeexperiences. It has been shown that both drug administration and exposure tostress induce adaptations at the level of synapses involving modifications inthe density and morphology of dendritic spines that are regulated, at least inpart, by a small GTPase known as Rac1. Evidence from our laboratory revealedthat repeated stress alters the capacity of a subsequentcocaine injection to modulate dendritic spine morphology and actin dynamics inthe NA core. Moreover, the pharmacological inhibition ofactin polymerization in the NA prevents stress cross-sensitization withcocaine. Thus, the main goal of this project is to evaluate whether changes inRac1 signaling induced by chronic stress, facilitate the development ofsensitization to cocaine. For this purpose, we have generated lentiviral particlescontaining a constitutive active form of Rac1 (CA-Rac1) to express in NA, andexplore its function during cross-sensitization between stress and cocaine.Thus, Wistar rats will be exposed to chronic restraint stress two hours dailyduring 7 days. Stressed and control animals will be administered with anintra-accumbens injection of CA-Rac1 before a challenge with cocaine, whenbehavioral sensitization will be evaluated. Our data suggests that the expressionof the active form of Rac1 is sufficient to prevent the expression ofcross-sensitization between stress and cocaine.