Ethanol withdrawal-induced brain metabolites and the pharmacological effects of acamprosate in mice lacking ENT1

David J. Hinton, Moonnoh R. Lee, Taylor L. Jacobson, Prasanna K. Mishra, Mark A Frye, David A. Mrazek, Slobodan I Macura, Doo Sup Choi

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Acamprosate is clinically used to treat alcohol-dependent patients. While the molecular and pharmacological mechanisms of acamprosate remain unclear, it has been shown to regulate γ-aminobutyric acid (GABA) or glutamate levels in the cortex and striatum. To investigate the effect of acamprosate on brain metabolites in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc), we employed in vivo 16.4 T proton magnetic resonance spectroscopy. We utilized type 1 equilibrative nucleoside transporter (ENT1) null mice since acamprosate attenuates ethanol drinking in these mice. Our findings demonstrated that ethanol withdrawal reduced GABA levels and increased phosphorylated choline compounds in the mPFC of both wild-type and ENT1 null mice. Notably, acamprosate normalized these withdrawal-induced changes only in ENT1 null mice. In the NAc, ethanol withdrawal increased glutamate and glutamine (Glx) levels only in wild-type mice. Interestingly, acamprosate reduced Glx levels in the NAc compared to the withdrawal state in both genotypes. These results provide a molecular basis for the pharmacological effect of acamprosate in the cortical-striatal circuit.

Original languageEnglish (US)
Pages (from-to)2480-2488
Number of pages9
JournalNeuropharmacology
Volume62
Issue number8
DOIs
StatePublished - Jun 2012

Fingerprint

Ethanol
Pharmacology
Brain
Nucleus Accumbens
Prefrontal Cortex
gamma-Aminobutyric Acid
Glutamic Acid
Equilibrative Nucleoside Transporter 1
Aminobutyrates
Corpus Striatum
Choline
acamprosate
Glutamine
Drinking
Genotype
Alcohols

Keywords

  • [ H] MRS
  • Acamprosate
  • ENT1
  • Ethanol withdrawal
  • GABA
  • Glutamate

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Ethanol withdrawal-induced brain metabolites and the pharmacological effects of acamprosate in mice lacking ENT1. / Hinton, David J.; Lee, Moonnoh R.; Jacobson, Taylor L.; Mishra, Prasanna K.; Frye, Mark A; Mrazek, David A.; Macura, Slobodan I; Choi, Doo Sup.

In: Neuropharmacology, Vol. 62, No. 8, 06.2012, p. 2480-2488.

Research output: Contribution to journalArticle

Hinton, David J. ; Lee, Moonnoh R. ; Jacobson, Taylor L. ; Mishra, Prasanna K. ; Frye, Mark A ; Mrazek, David A. ; Macura, Slobodan I ; Choi, Doo Sup. / Ethanol withdrawal-induced brain metabolites and the pharmacological effects of acamprosate in mice lacking ENT1. In: Neuropharmacology. 2012 ; Vol. 62, No. 8. pp. 2480-2488.
@article{87524641b9a440829927402aeb9f33bc,
title = "Ethanol withdrawal-induced brain metabolites and the pharmacological effects of acamprosate in mice lacking ENT1",
abstract = "Acamprosate is clinically used to treat alcohol-dependent patients. While the molecular and pharmacological mechanisms of acamprosate remain unclear, it has been shown to regulate γ-aminobutyric acid (GABA) or glutamate levels in the cortex and striatum. To investigate the effect of acamprosate on brain metabolites in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc), we employed in vivo 16.4 T proton magnetic resonance spectroscopy. We utilized type 1 equilibrative nucleoside transporter (ENT1) null mice since acamprosate attenuates ethanol drinking in these mice. Our findings demonstrated that ethanol withdrawal reduced GABA levels and increased phosphorylated choline compounds in the mPFC of both wild-type and ENT1 null mice. Notably, acamprosate normalized these withdrawal-induced changes only in ENT1 null mice. In the NAc, ethanol withdrawal increased glutamate and glutamine (Glx) levels only in wild-type mice. Interestingly, acamprosate reduced Glx levels in the NAc compared to the withdrawal state in both genotypes. These results provide a molecular basis for the pharmacological effect of acamprosate in the cortical-striatal circuit.",
keywords = "[ H] MRS, Acamprosate, ENT1, Ethanol withdrawal, GABA, Glutamate",
author = "Hinton, {David J.} and Lee, {Moonnoh R.} and Jacobson, {Taylor L.} and Mishra, {Prasanna K.} and Frye, {Mark A} and Mrazek, {David A.} and Macura, {Slobodan I} and Choi, {Doo Sup}",
year = "2012",
month = "6",
doi = "10.1016/j.neuropharm.2012.02.022",
language = "English (US)",
volume = "62",
pages = "2480--2488",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "Elsevier Limited",
number = "8",

}

TY - JOUR

T1 - Ethanol withdrawal-induced brain metabolites and the pharmacological effects of acamprosate in mice lacking ENT1

AU - Hinton, David J.

AU - Lee, Moonnoh R.

AU - Jacobson, Taylor L.

AU - Mishra, Prasanna K.

AU - Frye, Mark A

AU - Mrazek, David A.

AU - Macura, Slobodan I

AU - Choi, Doo Sup

PY - 2012/6

Y1 - 2012/6

N2 - Acamprosate is clinically used to treat alcohol-dependent patients. While the molecular and pharmacological mechanisms of acamprosate remain unclear, it has been shown to regulate γ-aminobutyric acid (GABA) or glutamate levels in the cortex and striatum. To investigate the effect of acamprosate on brain metabolites in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc), we employed in vivo 16.4 T proton magnetic resonance spectroscopy. We utilized type 1 equilibrative nucleoside transporter (ENT1) null mice since acamprosate attenuates ethanol drinking in these mice. Our findings demonstrated that ethanol withdrawal reduced GABA levels and increased phosphorylated choline compounds in the mPFC of both wild-type and ENT1 null mice. Notably, acamprosate normalized these withdrawal-induced changes only in ENT1 null mice. In the NAc, ethanol withdrawal increased glutamate and glutamine (Glx) levels only in wild-type mice. Interestingly, acamprosate reduced Glx levels in the NAc compared to the withdrawal state in both genotypes. These results provide a molecular basis for the pharmacological effect of acamprosate in the cortical-striatal circuit.

AB - Acamprosate is clinically used to treat alcohol-dependent patients. While the molecular and pharmacological mechanisms of acamprosate remain unclear, it has been shown to regulate γ-aminobutyric acid (GABA) or glutamate levels in the cortex and striatum. To investigate the effect of acamprosate on brain metabolites in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc), we employed in vivo 16.4 T proton magnetic resonance spectroscopy. We utilized type 1 equilibrative nucleoside transporter (ENT1) null mice since acamprosate attenuates ethanol drinking in these mice. Our findings demonstrated that ethanol withdrawal reduced GABA levels and increased phosphorylated choline compounds in the mPFC of both wild-type and ENT1 null mice. Notably, acamprosate normalized these withdrawal-induced changes only in ENT1 null mice. In the NAc, ethanol withdrawal increased glutamate and glutamine (Glx) levels only in wild-type mice. Interestingly, acamprosate reduced Glx levels in the NAc compared to the withdrawal state in both genotypes. These results provide a molecular basis for the pharmacological effect of acamprosate in the cortical-striatal circuit.

KW - [ H] MRS

KW - Acamprosate

KW - ENT1

KW - Ethanol withdrawal

KW - GABA

KW - Glutamate

UR - http://www.scopus.com/inward/record.url?scp=84862807936&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862807936&partnerID=8YFLogxK

U2 - 10.1016/j.neuropharm.2012.02.022

DO - 10.1016/j.neuropharm.2012.02.022

M3 - Article

VL - 62

SP - 2480

EP - 2488

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

IS - 8

ER -