Low brain histamine content affects ethanol-induced motor impairment

Minnamaija Lintunen, Kristiina Raatesalmi, Tina Sallmen, Oleg Anichtchik, Kaj Karlstedt, Jan Kaslin, Kalervo Kiianmaa, Esa R. Korpi, Pertti Panula

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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 α-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 ethanolsensitive rats. Brain histamine levels and possibly signaling via H3 receptors may thus correlate with genetic differences in ethanol-induced motor impairment.

Original languageEnglish
Pages (from-to)94-105
Number of pages12
JournalNeurobiology of Disease
Issue number1
Publication statusPublished - 2002
Externally publishedYes

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