title: Decreased GABA(A) benzodiazepine binding site densities in postmortem brains of Cloninger type 1 and 2 alcoholics.
abstract: Ethanol modulates the GABA(A) receptor to cause sedative, anxiolytic and hypnotic effects that are qualitatively similar to benzodiazepines and barbiturates. The aim of this study was to explore if GABA(A) receptor density is altered in post-mortem brains of anxiety-prone Cloninger type 1 and socially hostile type 2 alcoholic subtypes when compared to controls. The GABA(A) binding site density was measured by whole-hemisphere autoradiography with tritium labeled flunitrazepam ([(3)H]flunitrazepam) from 17 alcoholic (nine type 1, eight type 2) and 10 non-alcoholic post-mortem brains, using cold flumazepam as a competitive ligand. A total of eight specific brain areas were examined. Alcoholics displayed a significantly (p < 0.001, bootstrap type generalizing estimating equations model) reduced [(3)H]flunitrazepam binding site density when compared to controls. When localized, type 2 alcoholics displayed a significantly (p ≤ 0.05) reduced [(3)H]flunitrazepam binding site density in the internal globus pallidus, the gyrus dentatus and the hippocampus, whereas type 1 alcoholics differed from controls in the internal globus pallidus and the hippocampus. While previous reports have demonstrated significant alterations in dopaminergic and serotonergic receptors between type 1 and type 2 alcoholics among these same subjects, we observed no statistically significant difference in [(3)H]flunitrazepam binding site densities between the Cloninger type 1 and type 2 alcoholics.
authors: Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland.
authors: Virpi
authors: V
authors: Laukkanen
authors: Markus
authors: M
authors: Storvik
authors: Merja
authors: M
authors: Häkkinen
authors: Yumiko
authors: Y
authors: Akamine
authors: Erkki
authors: E
authors: Tupala
authors: Matti
authors: M
authors: Virkkunen
authors: Jari
authors: J
authors: Tiihonen
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000145:classification* / Q000378:metabolism* / Q000523:psychology; D001007:Anxiety; D001344:Autopsy; D001345:Autoradiography; D001923:Brain Chemistry; D018891:Dentate Gyrus / Q000737:chemistry; D005260:Female; D005445:Flunitrazepam / Q000378:metabolism; D005917:Globus Pallidus / Q000737:chemistry; D006624:Hippocampus / Q000737:chemistry; D006791:Hostility; D006801:Humans; D008297:Male; D008875:Middle Aged; D011963:Receptors, GABA-A / Q000032:analysis* / Q000378:metabolism; D014316:Tritium
chemical_list: D011963:Receptors, GABA-A; D014316:Tritium; D005445:Flunitrazepam