Decreased striatal monoaminergic terminals in severe chronic alcoholism demonstrated with (+)[11C]Dihydrotetrabenazine and positron emission tomography

Authors

  • Dr. Sid Gilman MD,

    Corresponding author
    1. Department of Neurology, University of Michigan, Ann Arbor, MI
    2. University of Michigan Alcohol Research Center, Ann Arbor, MI
    • Department of Neurology, University of Michigan Medical Center, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0316
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  • Robert A. Koeppe PhD,

    1. Division of Nuclear Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI
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  • Kenneth M. Adams PhD,

    1. University of Michigan Alcohol Research Center, Ann Arbor, MI
    2. Division of Neuropsychology, Department of Psychiatry, University of Michigan, Ann Arbor, MI
    3. Psychology Service, Ann Arbor Veterns Affairs Medical Center, Ann Arbor, MI
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  • Larry Junck MD,

    1. Department of Neurology, University of Michigan, Ann Arbor, MI
    2. University of Michigan Alcohol Research Center, Ann Arbor, MI
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  • Karen J. Kluin MS,

    1. Department of Neurology, University of Michigan, Ann Arbor, MI
    2. University of Michigan Alcohol Research Center, Ann Arbor, MI
    3. Division of Speech Pathology, Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, MI
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  • Doug Johnson-Greene PhD,

    1. Department of Physical Medicine and Rehabilitaion, Johns Hopkins University School of Medicine, Baltimore, MD
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  • Susan Martorello MS,

    1. Department of Neurology, University of Michigan, Ann Arbor, MI
    2. University of Michigan Alcohol Research Center, Ann Arbor, MI
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  • Mary Heumann BS,

    1. Department of Neurology, University of Michigan, Ann Arbor, MI
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  • Rajesh Bandekar MA

    1. University of Michigan Alcohol Research Center, Ann Arbor, MI
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Abstract

We used (+)[11C]dihydrotetrabenazine, a new ligand for the type 2 vesicular monoamine transporter, with positron emission tomography to study striatal monoaminergic presynaptic terminals in 7 male severe chronic alcoholic subjects without Wernicke–Korsakoff disease compared with 7 male normal controls of similar ages. We found reduced specific binding in the caudate nucleus and putamen in the alcoholic group, and the difference reached significance in the putamen. Specific binding was not decreased in the thalamus, which was examined as a reference structure. We also detected deficits in blood-to-brain transfer rate, K1, in the same regions of the alcoholic group, with a significant difference in the putamen. K1 was unchanged in the thalamus. The finding of reduced striatal VMAT2 in severe chronic alcoholic patients suggests that nigrostriatal monoaminergic terminals are reduced, with or without loss of neurons from the substantia nigra. The findings suggest that the damaging effects of severe chronic alcoholism on the central nervous system are more extensive than previously considered.

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