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

RIGONI, D.; AVALOS M.P; BISBAL, M.; CANCELA LILIANA M; BOLLATI, F.

Mar del plata

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

It is well known that there is ahigh rate of co-occurrence of substance abuse disorders and stressfullifeexperiences. It has been shown that both drug administration and exposure tostress induce adaptationsat the level of synapses involving modifications inthe density and morphology of dendritic spines thatare regulated, at least inpart, by a small GTPase known as Rac1. Evidence from our laboratoryrevealedthatrepeated stress alters the capacity of a subsequentcocaine injection to modulate dendriticspine morphology and actin dynamics inthe NA core. Moreover, the pharmacological inhibition ofactinpolymerization in the NA prevents stress cross-sensitization withcocaine. Thus, the main goal of this projectis to evaluate whether changes inRac1 signaling induced by chronic stress, facilitate the developmentofsensitization to cocaine. For this purpose, we have generated lentiviral particlescontaining a constitutiveactive form of Rac1 (CA-Rac1) to express in NA, andexplore its function during cross-sensitization betweenstress and cocaine.Thus, Wistar rats will be exposed to chronic restraint stress two hours dailyduring7 days. Stressed and control animals will be administered with anintra-accumbens injection of CA-Rac1before a challenge with cocaine, whenbehavioral sensitization will be evaluated. Our data suggests that theexpression of the active form of Rac1 is sufficient to prevent the expression ofcross-sensitization betweenstress and cocaine.