title: Increased metabotropic glutamate 2/3 receptor binding in the perigenual anterior cingulate cortex of Cloninger type 2 alcoholics: a whole-hemisphere autoradiography study.
abstract: OBJECTIVE
  Metabotropic glutamate receptors 2 and 3 (mGluR2/3) contribute to control the level of glutamate in the synapse. In rodents, mGluR2/3 agonists attenuate the reinstatement of alcohol-seeking behavior. Linking possible alterations of the mGluR2/3 system to the etiology and type of alcoholism could provide valuable information for the development of novel mGluR2/3 function modulating therapies in addiction treatment. To date, mGluR2/3 binding density has not been studied in human alcoholics. We aimed to investigate the possible differences in mGluR2/3 binding between Cloninger type 1 anxiety-prone and type 2 impulsive alcoholics and controls.
  
  
  METHODS
  We performed a post-mortem whole-hemisphere autoradiography to study the mGluR2/3 binding density of 9 type 1 alcoholics, 8 type 2 alcoholics and 10 controls. [(3)H]LY341495, a potent group II metabotropic glutamate receptor antagonist, was used as the radio-ligand with l-glutamate as a displacer.
  
  
  RESULTS
  [(3)H]LY341495 binding density was statistically significantly increased (P = 0.046) in the perigenual anterior cingulate cortex (pACC) of type 2 alcoholics when compared with controls. In other brain areas, no significant difference between the groups was found.
  
  
  CONCLUSIONS
  This preliminary study suggests that impulsive type 2 alcoholics might have alterations in the mGluR2/3 function in the pACC, a brain area presumed to be involved in the control of drug-seeking behaviors and self-control.
authors.affiliation: Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Niuvankuja 65, FI-70240 Kuopio, Finland Department of Psychiatry, Kuopio University Hospital, PO Box 1777, FI-70211 Kuopio, Finland.
authors.forename: Virpi
authors.initials: V
authors.lastname: Laukkanen
authors.affiliation: Department of Pharmacology and Toxicology, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Kärkkäinen
authors.affiliation: Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Niuvankuja 65, FI-70240 Kuopio, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Kupila
authors.affiliation: Unit of Primary Health Care, Helsinki University Central Hospital, FI-00014 Helsinki, Finland Department of General Practice, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Hannu
authors.initials: H
authors.lastname: Kautiainen
authors.affiliation: Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Niuvankuja 65, FI-70240 Kuopio, Finland Department of Clinical Neuroscience, Karolinska Institutet, Karolinska Sjukhuset, 17176 Stockholm, Sweden.
authors.forename: Jari
authors.initials: J
authors.lastname: Tiihonen
authors.affiliation: Department of Pharmacology and Toxicology, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland markus.storvik@uef.fi.
authors.forename: Markus
authors.initials: M
authors.lastname: Storvik
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000378:metabolism / Q000503:physiopathology*; D000596:Amino Acids / Q000494:pharmacology; D001345:Autoradiography; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D016022:Case-Control Studies; D005260:Female; D006179:Gyrus Cinguli / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D014966:Xanthenes / Q000494:pharmacology; D055815:Young Adult
chemical_list: D000596:Amino Acids; C114624:LY 341495; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3