Behavioral Effects of Cocaine Mediated by Nitric Oxide-GAPDH Transcriptional Signaling

作者：Xu Risheng; Serritella Anthony V; Sen Tanusree; Farook Justin M; Sedlak Thomas W; Baraban Jay; Snyder Solomon H^*; Sen Nilkantha

来源：Neuron, 2013, 78(4): 623-630.

DOI：10.1016/j.neuron.2013.03.021

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.

• 出版日期2013-5-22