Latrunculin A in the Nac Inhibited the Expression of Motor Sensitization and Increased AMPA Receptors after Cocaine in Chronically Stressed Animals.
Esparza, M.A.; Garcia Keller, C.; Virgolini, M.; Cancela L.M.
IFEC-CONICET, Universidad Nacional de Córdoba, Argentina
Haya de la Torre y Medina Allende, Ciudad Universitaria, Córdoba. CP:5000
Drug addiction is associated with long-term changes in the synaptic function, including the actin cytoskeleton. There is evidence about the proactive influence of stress on drug addiction. This study investigated whether the adaptations induced by repeated cocaine in the actin cytoskeleton, the surface expression of AMPA receptors (AMPAR), and the size of postsynaptic density (PSD) in the nucleus accumbens (NAc), occur and are relevant in a repeated immobilization stress-induced model of cocaine sensitization. The levels of F-actin, actin-binding protein (ABP) and AMPAR were determined by Western, and the size of PSD measured by electron microscopy. The effects of latrunculin A and CNQX in the NAc were studied on motor activity. In the NAc, a decrease in p-cofilin and p-cortactin, concomitant to an increase in AMPAR and the size of PSD, was found in the stress plus cocaine group. Latrunculin A in the NAc inhibited motor sensitization and increased AMPAR. This study shows that stress-induced changes in the actin cytoskeleton, the size of PSD and AMPAR partly parallel the alterations elicited by sensitization to repeated cocaine and that actin dynamics regulate AMPAR expression in the NAc and underlie the expression of cross-sensitization between stress and cocaine.
Grants: FONCYT, Ministerio de Ciencia y Tecnología, CONICET and SECyT (Córdoba Argentina)
