Frontiers in Neuroscience (Oct 2011)

Binge drinking: in search of its molecular target via the GABAA receptor

  • Andrew R.S.T. Yang,
  • Juan eLiu,
  • Heon S. Yi,
  • Kaitlin T. Warnock,
  • Mingfei eWang,
  • Harry L. June, Jr.,
  • Adam C. Puche,
  • Ahmed eElnabawi,
  • Werner eSieghart,
  • Laure eAurelian,
  • Harry L. June, Sr.,
  • Harry L. June, Sr.

DOI
https://doi.org/10.3389/fnins.2011.00123
Journal volume & issue
Vol. 5

Abstract

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Binge drinking, frequently referred to clinically as problem or hazardous drinking, is a pattern of excessive alcohol intake characterized by blood alcohol levels [BALs] > 0.08 g% within a 2 h period. Here, we show that overexpression of α1 subunits of the GABAA receptor contributes to binge drinking, and further document that this involvement is related to the neuroanatomical localization of 1 receptor subunits. Using a herpes simplex virus amplicon vector to deliver small interference RNA [siRNA], we showed that siRNA specific for the a1 subunit [pHSVsiLA1] caused profound, long-term, and selective reduction of gene expression, receptor density, and binge drinking in high alcohol drinking [HAD] rats when delivered into the ventral pallidum [VP]. Scrambled siRNA [pHSVsiNC] delivered similarly into the VP failed to alter gene expression, receptor density, or binge drinking. Silencing of the 1 gene in the VP, however, failed to alter binge sucrose or water intake. These results, along with our prior research, provide compelling evidence that the a1-containing GABAA receptor subunits are critical in the regulation of binge-like patterns of excessive drinking. Collectively, these data may be useful in the development of gene-based and novel pharmacological approaches for the treatment of excessive drinking.

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