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Exploring the Role of Central Astrocytic Glutamate Uptake in Ethanol Reward in Mice

Authors

  • Karen L. Smith,

    1. Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts
    2. Laboratory of Addictive Disorders, Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts
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  • Catherine S. John,

    1. Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts
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  • Elizabeth I. Sypek,

    1. Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts
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  • Dost Öngür,

    1. Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts
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  • Bruce M. Cohen,

    1. Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts
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  • Sarah M. Barry,

    1. Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts
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  • Anita J. Bechtholt

    Corresponding author
    1. Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts
    2. National Institute on Alcohol Abuse and Alcoholism , National Institutes of Health, Bethesda, Maryland
    • Reprint requests: Anita Bechtholt, PhD, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5635 Fishers Lane, Room 2056, Bethesda, MD 20892-9304; Tel.: 301-443-9334; Fax: 301-443-1650; E-mail: anita.bechtholt@gmail.com

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Abstract

Background

Alcoholism is associated with specific brain abnormalities revealed through postmortem studies, including a reduction in glial cell number and dysregulated glutamatergic neurotransmission. Whether these abnormalities contribute to the etiology of alcoholism, are consequences of alcohol use, or both is still unknown.

Methods

We investigated the role of astrocytic glutamate uptake in ethanol (EtOH) binge drinking in mice, using the “drinking in the dark” (DID) paradigm by blocking the astrocytic glutamate transporter (GLT-1) with intracerebroventricular (ICV) administration of dihydrokainic acid (DHK). To determine whether astrocytic glutamate uptake regulates the conditioned rewarding effects of EtOH, we examined the effects of ICV DHK on the acquisition and expression of EtOH-induced conditioned place preference.

Results

Blocking central astrocytic glutamate uptake selectively attenuated EtOH binge drinking behavior in mice. DHK did not alter the acquisition or expression of preference for EtOH-associated cues, indicating that reduced astrocytic glutamate trafficking may decrease binge-like drinking without altering the conditioned rewarding effects of EtOH.

Conclusions

Several alternative conclusions are plausible, however, interpreting these data in the context of the human literature, these findings suggest that the reduction of glia in the alcoholic brain may not be a predisposing factor to developing alcoholism and could be a consequence of EtOH toxicity that decreases excessive EtOH intake.

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