title: [³H]Ifenprodil binding in post-mortem brains of Cloninger type 1 and 2 alcoholics: a whole-hemisphere autoradiography study.
abstract: The glutamate N-methyl-d-aspartate (NMDA) receptor NR2B subunits are sensitive to ethanol and are found in brain areas related to ethanol addiction, dependence, development of alcohol tolerance, and alcohol withdrawal syndrome. Previous studies indicate that early-onset Cloninger type 2 alcoholics have an intact, responsive, dopaminergic system in the nucleus accumbens (NAC), whereas type 1 alcoholics have dopaminergic defects. NR2B-containing NMDA receptors in the NAC are involved in both non-opioid and opioid receptor-mediated reward. Our aim was to evaluate the putative [(3)H]ifenprodil binding alterations of NR2B receptors in limbic, hippocampal, and cortical brain areas of type 1 alcoholics (n=8), type 2 alcoholics (n=8), and control subjects (n=10) by postmortem whole hemisphere autoradiography. We found significantly different binding levels among these three subject groups, and the main difference was localized in the decreased binding in type 2 alcoholics and controls in the nucleus accumbens. Although preliminary and from relatively small diagnostic groups, these results suggest pathological alterations in the NR2B-mediated reward system of 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: Jukka
authors.initials: J
authors.lastname: Kupila
authors.affiliation: Pharmacology and Toxicology, Faculty of Health Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Kärkkäinen
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: Virpi
authors.initials: V
authors.lastname: Laukkanen
authors.affiliation: Pharmacology and Toxicology, Faculty of Health Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Merja
authors.initials: M
authors.lastname: Häkkinen
authors.affiliation: Unit of Primary Health Care, Helsinki University Central Hospital, Helsinki, Finland; Department of General Practice, University of Helsinki, Helsinki, Finland.
authors.forename: Hannu
authors.initials: H
authors.lastname: Kautiainen
authors.affiliation: Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jari
authors.initials: J
authors.lastname: Tiihonen
authors.affiliation: Pharmacology and Toxicology, Faculty of Health Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland. Electronic address: markus.storvik@uef.fi.
authors.forename: Markus
authors.initials: M
authors.lastname: Storvik
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D057229:Alcoholics / Q000145:classification*; D000437:Alcoholism / Q000145:classification* / Q000378:metabolism* / Q000473:pathology; D001345:Autoradiography; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009714:Nucleus Accumbens / Q000378:metabolism / Q000473:pathology; D010880:Piperidines / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000473:pathology; D055815:Young Adult
chemical_list: C121001:NR2B NMDA receptor; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C010739:ifenprodil
keywords: Addiction; Early-onset alcoholism; NMDA; NR2B; Withdrawal