title: Decreased [3H]naloxone Binding in the Dentate Gyrus of Cloninger Type 1 Anxiety-Prone Alcoholics: A Postmortem Whole-Hemisphere Autoradiography Study.
abstract: BACKGROUND
  The opioid system of the central nervous system plays an essential role in the regulation of the rewarding effects of alcohol. Alcohol affects mu-opioid receptor (MOR) function. Enhanced MOR function inhibits the GABAergic inhibition of the nucleus accumbens (Nac), which leads to a release of dopamine in the Nac. Of the few pharmaceutical treatments for alcoholism, the MOR antagonists naltrexone and nalmefene benefit most a subset of alcoholics who are characterized with early onset and impulsivity. Our aim was to investigate possible differences in the binding density of [³H]naloxone, a MOR competitive antagonist, between Cloninger type 1 anxiety-prone and harm-avoidant alcoholics, Cloninger type 2 impulsive and antisocial alcoholics, and healthy controls in brain areas that are essential for reward, learning, impulse-control, and mood regulation.
  
  
  METHODS
  We used postmortem whole-hemisphere autoradiography with [³H]naloxone, as a binding ligand. A subsequent autoradiography was performed with [³H]DAMGO, a selective MOR agonist.
  
  
  RESULTS
  Cloninger type 1 alcoholics displayed decreased [³H]naloxone binding density in all studied brain areas. This trend reached statistical significance in the dentate gyrus, where type 1 alcoholics' [³H]naloxone binding density was significantly decreased (p = 0.019) when compared to controls. A similar trend of decreased binding in type 1 alcoholics was observed in the [³H]DAMGO study.
  
  
  CONCLUSIONS
  Our finding suggest that Cloninger type 1 anxiety-prone alcoholics may have an altered [³H]naloxone binding in brain areas related to reward, impulse-control, mood, and learning. The finding lends support to the idea of Cloninger type 1 anxiety-prone alcoholics responding weaker to the opioidergic pharmaceuticals of the treatment of alcoholism than Cloninger type 2 impulsive alcoholics.
authors.affiliation: Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland.|Department of Psychiatry, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Virpi
authors.initials: V
authors.lastname: Laukkanen
authors.affiliation: Department of Pharmacology and Toxicology, University of Eastern Finland, Kuopio, Finland.
authors.forename: Olli
authors.identifier: http://orcid.org/0000-0003-0825-4956
authors.initials: O
authors.lastname: Kärkkäinen
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, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland.|Department of Clinical Neuroscience, Karolinska Institutet, Karolinska sjukhuset, Stockholm, Sweden.
authors.forename: Jari
authors.initials: J
authors.lastname: Tiihonen
authors.affiliation: Department of Pharmacology and Toxicology, University of Eastern Finland, Kuopio, Finland.
authors.forename: Markus
authors.initials: M
authors.lastname: Storvik
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D057229:Alcoholics; D000437:Alcoholism / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D001007:Anxiety / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D001344:Autopsy; D001345:Autoradiography; D018891:Dentate Gyrus / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000378:metabolism*; D009292:Narcotic Antagonists / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D014316:Tritium / Q000378:metabolism; D055815:Young Adult
chemical_list: D009292:Narcotic Antagonists; D014316:Tritium; D009270:Naloxone
keywords: Alcoholism; Autoradiography; Cloninger's Typology; Dentate Gyrus; Mu-Opioid Receptor