title: AMPA receptors in post-mortem brains of Cloninger type 1 and 2 alcoholics: a whole-hemisphere autoradiography study.
abstract: Dysfunction of the brain glutamate system has been associated with alcoholism. Ionotropic glutamatergic alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) play an important role in both neurotransmission and post-synaptic plasticity. Alterations in AMPAR densities may also play a role in the neurobiological changes associated with alcoholism. In the present study, [(3)H] AMPA binding density was evaluated in the nucleus accumbens (NAc), frontal cortex, anterior cingulate cortex (ACC), dentate gyrus and hippocampus of Cloninger type 1 (n=9) and 2 (n=8) alcoholics, and compared with non-alcoholic control subjects (n=10) by post-mortem whole-hemisphere autoradiography. The [(3)H] AMPA binding density was significantly higher in the ACC of early onset type 2 alcoholics when compared with controls (p=0.011). There was also a significant negative correlation between [(3)H] AMPA binding and previously published results of dopamine transporter (DAT) density in the ACC in these same brain samples (R=-0.95, p=0.001). Although preliminary, and from a relatively small diagnostic group, the present results help to further explain the pathology of alcohol dependence and impulsive behaviour in type 2 alcoholics.
authors.affiliation: Pharmacology and Toxicology, Faculty of Health Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland; Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Kärkkäinen
authors.forename: Jukka
authors.initials: J
authors.lastname: Kupila
authors.forename: Merja
authors.initials: M
authors.lastname: Häkkinen
authors.forename: Virpi
authors.initials: V
authors.lastname: Laukkanen
authors.forename: Erkki
authors.initials: E
authors.lastname: Tupala
authors.forename: Hannu
authors.initials: H
authors.lastname: Kautiainen
authors.forename: Jari
authors.initials: J
authors.lastname: Tiihonen
authors.forename: Markus
authors.initials: M
authors.lastname: Storvik
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000437:Alcoholism / Q000145:classification* / Q000378:metabolism*; D001344:Autopsy; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018091:Receptors, AMPA / Q000378:metabolism*
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D018091:Receptors, AMPA
keywords: Addiction; Alcohol dependence; Alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid; Anterior cingulate cortex; Early onset alcoholism; Impulsive behavior