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.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Dietz DM,Sun H,Lobo MK,Cahill ME,Chadwick B,Gao V,Koo JW,Mazei-Robison MS,Dias C,Maze I,Damez-Werno D,Dietz KC,Scobie KN,Ferguson D,Christoffel D,Ohnishi Y,Hodes GE,Zheng Y,Neve RL,Hahn KM,Russo SJ,Nestler EJdoi
10.1038/nn.3094subject
Has Abstractpub_date
2012-06-01 00:00:00pages
891-6issue
6eissn
1097-6256issn
1546-1726pii
nn.3094journal_volume
15pub_type
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