Acamprosate reduces ethanol drinking behaviors and alters the metabolite profile in mice lacking ENT1.

Abstract

Acamprosate is clinically used to treat alcoholism. However, the precise molecular functionality of acamprosate in the central nervous system remains unclear, although it is known to antagonize glutamate action in the brain. Since elevated glutamate signaling, especially in the nucleus accumbens (NAc), is implicated in several aspects of alcoholism, we utilized mice lacking type 1 equilibrative nucleoside transporter (ENT1), which exhibit increased glutamate levels in the NAc as well as increased ethanol drinking behaviors. We found that acamprosate significantly reduced ethanol drinking of mice lacking ENT1 (ENT1(-/-)) while having no such effect in wild-type littermates. We then analyzed the basal and acamprosate-treated accumbal metabolite profiles of ENT1(-/-) and wild-type mice using in vivo 16.4T proton magnetic resonance spectroscopy (MRS). Our data show that basal glutamate+glutamine (Glx), glutamate, glutamine and N-acetylaspartatic acid (NAA) levels are increased in the nucleus accumbens (NAc) of ENT1(-/-) compared to wild-type mice. We then found that acamprosate treatment significantly reduced Glx and glutamine levels while increasing taurine levels in the NAc of only ENT1(-/-) compared to their saline-treated group while normalizing other metabolite compared to wild-type mice. This study will be useful in the understanding of the molecular basis of acamprosate in the brain.

• Authors: Moonnoh R Lee, David J Hinton, Jinhua Wu, Prasanna K Mishra, John D Port, Slobodan I Macura, Doo-Sup Choi
• Journal: Neuroscience letters (Neurosci Lett) Vol. 490 Issue 2 Pg. 90-5 (Feb 25 2011) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 21172405 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Equilibrative Nucleoside Transporter 1
• SLC29A1 protein, mouse
• Taurine
• Ethanol
• Glutamic Acid
• Acamprosate

Topics

• Acamprosate
• Alcohol Drinking (drug therapy, genetics, metabolism)
• Animals
• Equilibrative Nucleoside Transporter 1 (genetics, metabolism)
• Ethanol (administration & dosage)
• Glutamic Acid (biosynthesis)
• Male
• Metabolome (drug effects, genetics, physiology)
• Mice
• Mice, 129 Strain
• Mice, Inbred C57BL
• Mice, Knockout
• Nucleus Accumbens (drug effects, metabolism)
• Taurine (analogs & derivatives, pharmacology)
• Up-Regulation (genetics)