title: Decreased striatal monoaminergic terminals in severe chronic alcoholism demonstrated with (+)[11C]dihydrotetrabenazine and positron emission tomography.
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.
authors.affiliation: Department of Neurology, University of Michigan, and University of Michigan Alcohol Research Center, Ann Arbor, USA.
authors.forename: S
authors.initials: S
authors.lastname: Gilman
authors.forename: R A
authors.initials: RA
authors.lastname: Koeppe
authors.forename: K M
authors.initials: KM
authors.lastname: Adams
authors.forename: L
authors.initials: L
authors.lastname: Junck
authors.forename: K J
authors.initials: KJ
authors.lastname: Kluin
authors.forename: D
authors.initials: D
authors.lastname: Johnson-Greene
authors.forename: S
authors.initials: S
authors.lastname: Martorello
authors.forename: M
authors.initials: M
authors.lastname: Heumann
authors.forename: R
authors.initials: R
authors.lastname: Bandekar
mesh_terms: D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000378:metabolism / Q000503:physiopathology*; D015306:Biogenic Monoamines / Q000378:metabolism; D015331:Cohort Studies; D003342:Corpus Striatum / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009411:Nerve Endings / Q000378:metabolism / Q000503:physiopathology*; D009479:Neuropeptides; D018377:Neurotransmitter Agents / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects; D013747:Tetrabenazine / Q000031:analogs & derivatives*; D014055:Tomography, Emission-Computed; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
chemical_list: D015306:Biogenic Monoamines; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; C493452:SLC18A2 protein, human; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; C032811:dihydrotetrabenazine; D013747:Tetrabenazine