Stress-induced sensitization to cocaine:actin cytoskeleton remodeling within mesocorticolimbic nuclei

ESPARZA M.A.; BOLLATI F; GARCIA-KELLER C; VIRGOLINI M B; LOPEZ L M; BRUSCO A; SHEN H-W; KALIVAS P W; CANCELA L M

EUROPEAN JOURNAL OF NEUROSCIENCE

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2012 p. 1 - 15

0953-816X

This studyi nvestigated the consequence of repeated   stress on actin cytoskeleton remodeling in the nucleus accumbens (NAc) and prefrontal cortex (Pfc), and the involvement of  this remodeling in the expression ofs tress-induced motor cross-sensitization with cocaine. Wistar rats were restrained daily (2h) for 7 days and, 3 weeks later, their NAc and Pfc were dissected 45 min after acute saline or cocaine (30mg/kg i.p.). F-actin, actin-binding proteins (ABP) and GluR1 were quantified by Western blotting, and dendritic spines and postsynaptic density (PSD) size measured by electronmicroscopy. In the NAc from the stress plus cocaine group we observed a decrease in the phosphorylation of two ABPs, cofilin and cortactin, and an increase in the PSD size and the surface expression of GluR1, consistent with a more highly branched actin cytoskeleton. The Pfc also showed evidence of Increased actin polymerization after stress as an increase was observed in Arp2, and in the  number of spines. Inhibiting actin cycling and polymerization with latrunculin A into the NAc, but not the Pfc, inhibited thee xpression of cross-sensitization to cocaine (15mg/kg i.p.) and restored the expression of GluR1 to control levels. This study shows that a history of repeated stress alters the ability of a subsequent cocaine injection to modulate dendritic spine morphology, actin dynamics an dGluR1expression in the NAc. Furthermore, by regulating GluR1 xpression int he NAc, elevated actin cycling contributes to the expression of cross-sensitization between stress and cocaine, while stress-induced changes in the Pfc were not associated with cross-sensitization.