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

  • Neuron. 2013 May 22;78(4):623-30. doi: 10.1016/j.neuron.2013.03.021.
Risheng Xu  1 ,  Anthony V Serritella ,  Tanusree Sen ,  Justin M Farook ,  Thomas W Sedlak ,  Jay Baraban ,  Solomon H Snyder ,  Nilkantha Sen
Affiliations
  • 1. The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
PMID: 23719162 DOI: 10.1016/j.neuron.2013.03.021
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.

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