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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 Hahn | Scott J Russo | Eric J Nestler
Nature neuroscience | 2012

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.

Pubmed ID: 22522400

Research resources used in this publication

None found

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Antibodies used in this publication

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Associated grants

  • Agency: NIDA NIH HHS, United States
    Id: P01 DA008227
  • Agency: NIMH NIH HHS, United States
    Id: K99 MH094405
  • Agency: NIDA NIH HHS, United States
    Id: R01 DA014133-12
  • Agency: NIDA NIH HHS, United States
    Id: P01 DA008227-21
  • Agency: NIDA NIH HHS, United States
    Id: R01 DA014133-11
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH051399
  • Agency: NIDA NIH HHS, United States
    Id: R01 DA14133
  • Agency: NIDA NIH HHS, United States
    Id: R01 DA014133
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH051399-11
  • Agency: NIDA NIH HHS, United States
    Id: R01 DA014133-13
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH51399
  • Agency: NIDA NIH HHS, United States
    Id: P01 DA08227
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH051399-10

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This is a list of tools and resources that we have found mentioned in this publication.


NeuronStudio (tool)

RRID:SCR_013798

A software application which allows reconstruction of neuronal structures from confocal and multi-photon images. NeuronStudio provides tools for manual, semi-manual, and automatic tracing of the dendritic arbor, as well as manual and automatic detection and classification of dendritic spines. Advanced 2D and 3D visualization techniques facilitate the verification of the reconstruction, as well as allowing accurate manual editing. The most current version is Version 0.9.92 which was last updated on November 19, 2009.

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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