Low brain histamine content affects ethanol-induced motor impairment.
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.
Lintunen
Minnamaija
M
Department of Biology, Abo Akademi University, Turku, Finland.
Raatesalmi
Kristiina
K
Sallmen
Tina
T
Anichtchik
Oleg
O
Karlstedt
Kaj
K
Kaslin
Jan
J
Kiianmaa
Kalervo
K
Korpi
Esa R
ER
Panula
Pertti
P
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
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