Acute effects of acamprosate and MPEP on ethanol drinking-in-the-dark in male C57BL/6J mice

Tripta Gupta, Yaqoob M. Syed, Andrew A. Revis, Samantha A. Miller, Marina Martinez, Kellen A. Cohn, Michael R. Demeyer, Kevin Y. Patel, Weronika J. Brzezinska, Justin S. Rhodes

Research output: Contribution to journalArticle

Abstract

Background: Recently, a simple procedure in mice, Drinking-in-the-Dark (DID), was hypothesized to have value for medication development for human alcoholism. In DID, mice are offered intermittent, limited access to ethanol over a series of days during the dark phase that results in rapid drinking to intoxication in predisposed genotypes. Methods: We measured the effects of acamprosate or MPEP, metabotropic glutamate 5 receptor (mGluR5) antagonist, on intake of 20% ethanol, plain tap water or 10% sugar water using the DID procedure in male C57BL/6J mice. Results: Acamprosate (100, 200, 300, or 400 mg/kg) dose dependently decreased ethanol drinking with 300 mg/kg reducing ethanol intake by approximately 20% without affecting intake of plain water or 10% sugar water. MPEP (1, 3, 5, 10, 20, or 40 mg/kg) was more potent than acamprosate with 20 mg/kg reducing ethanol intake by approximately 20% and for longer duration without affecting intake of plain water or 10% sugar water. Conclusions: These results support the hypothesis that mGluR5 signaling plays a role in excessive ethanol intake in DID and suggest DID may have value for screening novel compounds that reduce overactive glutamate signaling for potential pharmaceutical treatment of excessive ethanol drinking behavior.

Original languageEnglish (US)
Pages (from-to)1992-1998
Number of pages7
JournalAlcoholism: Clinical and Experimental Research
Volume32
Issue number11
DOIs
StatePublished - Nov 1 2008

Keywords

  • Acamprosate
  • Alcoholism
  • C57BL/6J
  • Drinking
  • Ethanol
  • Glutamate
  • MPEP
  • Metabotropic glutamate receptor 5
  • mGluR5

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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    Gupta, T., Syed, Y. M., Revis, A. A., Miller, S. A., Martinez, M., Cohn, K. A., Demeyer, M. R., Patel, K. Y., Brzezinska, W. J., & Rhodes, J. S. (2008). Acute effects of acamprosate and MPEP on ethanol drinking-in-the-dark in male C57BL/6J mice. Alcoholism: Clinical and Experimental Research, 32(11), 1992-1998. https://doi.org/10.1111/j.1530-0277.2008.00787.x