title: Rac1 is essential in cocaine-induced structural plasticity of nucleus accumbens neurons.
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.
authors.affiliation: Fishberg Department of Neuroscience and Friedman Brain Institute, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Dietz
authors.forename: Haosheng
authors.initials: H
authors.lastname: Sun
authors.forename: Mary Kay
authors.initials: MK
authors.lastname: Lobo
authors.forename: Michael E
authors.initials: ME
authors.lastname: Cahill
authors.forename: Benjamin
authors.initials: B
authors.lastname: Chadwick
authors.forename: Virginia
authors.initials: V
authors.lastname: Gao
authors.forename: Ja Wook
authors.initials: JW
authors.lastname: Koo
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Mazei-Robison
authors.forename: Caroline
authors.initials: C
authors.lastname: Dias
authors.forename: Ian
authors.initials: I
authors.lastname: Maze
authors.forename: Diane
authors.initials: D
authors.lastname: Damez-Werno
authors.forename: Karen C
authors.initials: KC
authors.lastname: Dietz
authors.forename: Kimberly N
authors.initials: KN
authors.lastname: Scobie
authors.forename: Deveroux
authors.initials: D
authors.lastname: Ferguson
authors.forename: Daniel
authors.initials: D
authors.lastname: Christoffel
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ohnishi
authors.forename: Georgia E
authors.initials: GE
authors.lastname: Hodes
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.forename: Rachael L
authors.initials: RL
authors.lastname: Neve
authors.forename: Klaus M
authors.initials: KM
authors.lastname: Hahn
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Russo
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Nestler
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders; D049229:Dendritic Spines / Q000187:drug effects* / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein
chemical_list: D018765:Dopamine Uptake Inhibitors; D009479:Neuropeptides; C484602:Rac1 protein, mouse; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D003042:Cocaine