The type 1 equilibrative nucleoside transporter regulates ethanol intoxication and preference

Doo Sup Choi, Maria Grazia Cascini, William Mailliard, Hannah Young, Peter Paredes, Thomas McMahon, Ivan Diamond, Antonello Bonci, Robert O. Messing

Research output: Contribution to journalArticle

188 Scopus citations

Abstract

Adenosine is an important mediator of ethanol intoxication. In vitro, ethanol stimulates adenosine signaling by inhibiting the type 1 equilibrative nucleoside transporter (ENT1), whereas chronic ethanol exposure downregulates ENT1. It is not known, however, whether ENT1 is important for ethanol intoxication or consumption in vivo. Here we report that ENT1-null mice show reduced hypnotic and ataxic responses to ethanol and greater consumption of alcohol as compared with their wild-type littermates. These features are associated with a decrease in adenosine tone, as measured indirectly as a reduction in A1 receptor-mediated inhibition of glutamate excitatory postsynaptic currents (EPSCs) in the nucleus accumbens, leading to increased phosphorylation of CRE-binding protein (CREB) in the striatum. Treatment with an A1 receptor agonist decreases EPSC amplitude and reduces ethanol consumption in ENT1-null mice. Our results indicate that ENT1 has a physiological role in ethanol-mediated behaviors and suggest that decreased A1 adenosine receptor function promotes alcohol consumption.

Original languageEnglish (US)
Pages (from-to)855-861
Number of pages7
JournalNature Neuroscience
Volume7
Issue number8
DOIs
StatePublished - Aug 1 2004

ASJC Scopus subject areas

  • Neuroscience(all)

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    Choi, D. S., Cascini, M. G., Mailliard, W., Young, H., Paredes, P., McMahon, T., Diamond, I., Bonci, A., & Messing, R. O. (2004). The type 1 equilibrative nucleoside transporter regulates ethanol intoxication and preference. Nature Neuroscience, 7(8), 855-861. https://doi.org/10.1038/nn1288