title: Low brain histamine content affects ethanol-induced motor impairment.
abstract: The effect of ethanol on motor performance in humans is well established but how neural mechanisms are affected by ethanol action remains largely unknown. To investigate whether the brain histaminergic system is important in it, we used a genetic model consisting of rat lines selectively outbred for differential ethanol sensitivity. Ethanol-sensitive rats had lower levels of brain histamine and lower densities of histamine-immunoreactive fibers than ethanol-insensitive rats, although both rat lines showed no changes in histamine synthesizing neurons. Lowering the high brain histamine content of the ethanol-insensitive rats with alpha-fluoromethylhistidine before ethanol administration increased their ethanol sensitivity in a behavioral motor function test. Higher H3 receptor ligand binding and histamine-induced G-protein activation was detected in several brain regions of ethanol-naive ethanol-sensitive rats. Brain histamine levels and possibly signaling via H3 receptors may thus correlate with genetic differences in ethanol-induced motor impairment.
authors.affiliation: Department of Biology, Abo Akademi University, Turku, Finland.
authors.forename: Minnamaija
authors.initials: M
authors.lastname: Lintunen
authors.forename: Kristiina
authors.initials: K
authors.lastname: Raatesalmi
authors.forename: Tina
authors.initials: T
authors.lastname: Sallmen
authors.forename: Oleg
authors.initials: O
authors.lastname: Anichtchik
authors.forename: Kaj
authors.initials: K
authors.lastname: Karlstedt
authors.forename: Jan
authors.initials: J
authors.lastname: Kaslin
authors.forename: Kalervo
authors.initials: K
authors.lastname: Kiianmaa
authors.forename: Esa R
authors.initials: ER
authors.lastname: Korpi
authors.forename: Pertti
authors.initials: P
authors.lastname: Panula
mesh_terms: D000437:Alcoholism / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D021461:Animals, Outbred Strains; D001345:Autoradiography; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D006632:Histamine / Q000378:metabolism*; D006639:Histidine / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000235:genetics; D008297:Male; D008762:Methylhistidines / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009412:Nerve Fibers / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011969:Receptors, Histamine H1 / Q000235:genetics; D011970:Receptors, Histamine H2 / Q000235:genetics; D018100:Receptors, Histamine H3 / Q000378:metabolism; D013462:Sulfur Radioisotopes
chemical_list: D002492:Central Nervous System Depressants; D004791:Enzyme Inhibitors; D008762:Methylhistidines; D012333:RNA, Messenger; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D018100:Receptors, Histamine H3; D013462:Sulfur Radioisotopes; D000431:Ethanol; D006639:Histidine; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D019204:GTP-Binding Proteins; D006640:Histidine Decarboxylase