title: Behavioral effects of cocaine mediated by nitric oxide-GAPDH transcriptional signaling.
abstract: Cocaine's behavioral-stimulant effects derive from potentiation of synaptic signaling by dopamine and serotonin leading to transcriptional alterations in postsynaptic cells. We report that a signaling cascade involving nitric oxide (NO) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mediates cocaine's transcriptional and behavioral actions. Lower, behavioral-stimulant doses enhance the cAMP response element-binding (CREB) signaling system, while higher, neurotoxic doses stimulate the p53 cytotoxic system. The drug CGP3466B, which potently and selectively blocks GAPDH nitrosylation and GAPDH-Siah binding, prevents these actions as well as behavioral effects of cocaine providing a strategy for anticocaine therapy.
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Risheng
authors.initials: R
authors.lastname: Xu
authors.forename: Anthony V
authors.initials: AV
authors.lastname: Serritella
authors.forename: Tanusree
authors.initials: T
authors.lastname: Sen
authors.forename: Justin M
authors.initials: JM
authors.lastname: Farook
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Sedlak
authors.forename: Jay
authors.initials: J
authors.lastname: Baraban
authors.forename: Solomon H
authors.initials: SH
authors.lastname: Snyder
authors.forename: Nilkantha
authors.initials: N
authors.lastname: Sen
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000697:Central Nervous System Stimulants; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); D003042:Cocaine