Loss of Dopamine D2 Receptors Induces Atrophy in the Temporal and Parietal Cortices and the Caudal Thalamus of Ethanol-Consuming Mice

Authors

  • Foteini Delis,

    1. From the Laboratory of Neuroimaging (FD, NDV, PKT), National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, Maryland; Behavioral Neuropharmacology and Neuroimaging Lab (FD, G-JW, PKT), Medical Department, Brookhaven National Laboratory, Upton, New York; Department of Anesthesiology (HB), Stony Brook University, Stony Brook, New York; Department of Biomedical Engineering (MX), Stony Brook University, Stony Brook, New York; Department of Physiology and Pharmacology (DG), Oregon Health and Sciences University, Portland, Oregon; and Department of Psychology (PKT), Stony Brook University, Stony Brook, New York.
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  • Helene Benveniste,

    1. From the Laboratory of Neuroimaging (FD, NDV, PKT), National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, Maryland; Behavioral Neuropharmacology and Neuroimaging Lab (FD, G-JW, PKT), Medical Department, Brookhaven National Laboratory, Upton, New York; Department of Anesthesiology (HB), Stony Brook University, Stony Brook, New York; Department of Biomedical Engineering (MX), Stony Brook University, Stony Brook, New York; Department of Physiology and Pharmacology (DG), Oregon Health and Sciences University, Portland, Oregon; and Department of Psychology (PKT), Stony Brook University, Stony Brook, New York.
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  • Michalis Xenos,

    1. From the Laboratory of Neuroimaging (FD, NDV, PKT), National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, Maryland; Behavioral Neuropharmacology and Neuroimaging Lab (FD, G-JW, PKT), Medical Department, Brookhaven National Laboratory, Upton, New York; Department of Anesthesiology (HB), Stony Brook University, Stony Brook, New York; Department of Biomedical Engineering (MX), Stony Brook University, Stony Brook, New York; Department of Physiology and Pharmacology (DG), Oregon Health and Sciences University, Portland, Oregon; and Department of Psychology (PKT), Stony Brook University, Stony Brook, New York.
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  • David Grandy,

    1. From the Laboratory of Neuroimaging (FD, NDV, PKT), National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, Maryland; Behavioral Neuropharmacology and Neuroimaging Lab (FD, G-JW, PKT), Medical Department, Brookhaven National Laboratory, Upton, New York; Department of Anesthesiology (HB), Stony Brook University, Stony Brook, New York; Department of Biomedical Engineering (MX), Stony Brook University, Stony Brook, New York; Department of Physiology and Pharmacology (DG), Oregon Health and Sciences University, Portland, Oregon; and Department of Psychology (PKT), Stony Brook University, Stony Brook, New York.
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  • Gene-Jack Wang,

    1. From the Laboratory of Neuroimaging (FD, NDV, PKT), National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, Maryland; Behavioral Neuropharmacology and Neuroimaging Lab (FD, G-JW, PKT), Medical Department, Brookhaven National Laboratory, Upton, New York; Department of Anesthesiology (HB), Stony Brook University, Stony Brook, New York; Department of Biomedical Engineering (MX), Stony Brook University, Stony Brook, New York; Department of Physiology and Pharmacology (DG), Oregon Health and Sciences University, Portland, Oregon; and Department of Psychology (PKT), Stony Brook University, Stony Brook, New York.
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  • Nora D. Volkow,

    1. From the Laboratory of Neuroimaging (FD, NDV, PKT), National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, Maryland; Behavioral Neuropharmacology and Neuroimaging Lab (FD, G-JW, PKT), Medical Department, Brookhaven National Laboratory, Upton, New York; Department of Anesthesiology (HB), Stony Brook University, Stony Brook, New York; Department of Biomedical Engineering (MX), Stony Brook University, Stony Brook, New York; Department of Physiology and Pharmacology (DG), Oregon Health and Sciences University, Portland, Oregon; and Department of Psychology (PKT), Stony Brook University, Stony Brook, New York.
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  • Panayotis K. Thanos

    1. From the Laboratory of Neuroimaging (FD, NDV, PKT), National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, Maryland; Behavioral Neuropharmacology and Neuroimaging Lab (FD, G-JW, PKT), Medical Department, Brookhaven National Laboratory, Upton, New York; Department of Anesthesiology (HB), Stony Brook University, Stony Brook, New York; Department of Biomedical Engineering (MX), Stony Brook University, Stony Brook, New York; Department of Physiology and Pharmacology (DG), Oregon Health and Sciences University, Portland, Oregon; and Department of Psychology (PKT), Stony Brook University, Stony Brook, New York.
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Reprint requests: Panayotis K. Thanos, Behavioral Neuropharmacology and Neuroimaging Lab, Medical Department, Brookhaven National Laboratory, 30 Bell Avenue, Building 490, Upton, NY 11973; Tel.: 631-344-7364; Fax: 631-344-2664; E-mail: thanos@bnl.gov

Abstract

Background:  The need of an animal model of alcoholism becomes apparent when we consider the genetic diversity of the human populations, an example being dopamine D2 receptor (DRD2) expression levels. Research suggests that low DRD2 availability is associated with alcohol abuse, while higher DRD2 levels may be protective against alcoholism. This study aims to establish whether (i) the ethanol-consuming mouse is a suitable model of alcohol-induced brain atrophy and (ii) DRD2 protect the brain against alcohol toxicity.

Methods:  Adult Drd2+/+ and Drd2−/− mice drank either water or 20% ethanol solution for 6 months. At the end of the treatment period, the mice underwent magnetic resonance (MR) imaging under anesthesia. MR images were registered to a common space, and regions of interest were manually segmented.

Results:  We found that chronic ethanol intake induced a decrease in the volume of the temporal and parietal cortices as well as the caudal thalamus in Drd2−/− mice.

Conclusions:  The result suggests that (i) normal DRD2 expression has a protective role against alcohol-induced brain atrophy and (ii) in the absence of Drd2 expression, prolonged ethanol intake reproduces a distinct feature of human brain pathology in alcoholism, the atrophy of the temporal and parietal cortices.

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