Behavioral effects of cocaine mediated by nitric oxide-GAPDH transcriptional signaling

Risheng Xu, Anthony V. Serritella, Tanusree Sen, Justin M. Farook, Thomas W. Sedlak, Jay Baraban, Solomon H. Snyder, Nilkantha Sen

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


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

Original languageEnglish (US)
Pages (from-to)623-630
Number of pages8
Issue number4
StatePublished - May 22 2013
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)


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