Rac1 is essential for the expression of behavioral sensitization induced by chronic stress in nucleus accumbens

RIGONI DAIANA; AVALOS MARIA PAULA; GUZMAN ANDREA SUSANA; BISBAL MARIANO; CANCELA LILIANA M; BOLLATI FLAVIA

Mar del Plata

Congreso; XXXII Congreso de la Sociedad Argentina de Investigación en Neurociencias. Congreso International.; 2017

Sociedad Argentina de Investigación en Neurociencias

It is well known that there is a high rate of co-occurrence of substance abuse disorders and stressful life experiences. It has been shown that both drug administration and exposure to stress induce adaptations at the level of synapses involving modifications in the density and morphology of dendritic spines that are regulated, at least in part, by a small GTPase known as Rac1. Evidence from our laboratory revealed that repeated stress alters the capacity of a subsequent cocaine injection to modulate dendritic spine morphology and actin dynamics in the NA core. Moreover, the pharmacological inhibition of actin polymerization in the NA prevents stress cross-sensitization with cocaine. Thus, the main goal of this project is to evaluate whether changes in Rac1 signaling induced by chronic stress, facilitate the development of sensitization to cocaine. For this purpose, we have generated lentiviral particles containing a constitutive active form of Rac1 (CA-Rac1) to express 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 CA-Rac1 before a challenge with cocaine, when behavioral sensitization will be evaluated. Our data suggests that the expression of the active form of Rac1 is sufficient to prevent the expression of cross-sensitization between stress and cocaine.