Rac1 is essential in cocaine-induced structural plasticity of nucleus accumbens neurons

David M. Dietz, Haosheng Sun, Mary Kay Lobo, Michael E. Cahill, Benjamin Chadwick, Virginia Gao, Ja Wook Koo, Michelle S. Mazei-Robison, Caroline Dias, Ian Maze, Diane Damez-Werno, Karen C. Dietz, Kimberly N. Scobie, Deveroux Ferguson, Daniel Christoffel, Yoko Ohnishi, Georgia E. Hodes, Yi Zheng, Rachael L. Neve, Klaus M. HahnScott J. Russo, Eric J. Nestler

Research output: Contribution to journalArticlepeer-review

127 Scopus citations

Abstract

Repeated cocaine administration increases the dendritic arborization of nucleus accumbens neurons, but the underlying signaling events remain unknown. Here we show that repeated exposure to cocaine negatively regulates the active form of Rac1, a small GTPase that controls actin remodeling in other systems. Further, we show, using viral-mediated gene transfer, that overexpression of a dominant negative mutant of Rac1 or local knockout of Rac1 is sufficient to increase the density of immature dendritic spines on nucleus accumbens neurons, whereas overexpression of a constitutively active Rac1 or light activation of a photoactivatable form of Rac1 blocks the ability of repeated cocaine exposure to produce this effect. Downregulation of Rac1 activity likewise promotes behavioral responses to cocaine exposure, with activation of Rac1 producing the opposite effect. These findings establish that Rac1 signaling mediates structural and behavioral plasticity in response to cocaine exposure.

Original languageEnglish (US)
Pages (from-to)891-896
Number of pages6
JournalNature neuroscience
Volume15
Issue number6
DOIs
StatePublished - Jun 2012
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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