Effects of (S)-alpha-fluoromethylhistidine and (R)-alpha-methylhistamine on locomotion of W/Wv mice |
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Authors: | N Sakai S Yamazaki K Onodera K Yanai K Maeyama T Watanabe |
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Affiliation: | Department of Pharmacology 1, Tohoku University School of Medicine, Sendai, Japan. |
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Abstract: | We studied the effects of inactivators of the central histaminergic neuron system, (R)-alpha-methylhistamine, a histamine H3 receptor agonist, and (S)-alpha-fluoromethylhistidine, a histamine synthesis inhibitor, on locomotor activity and brain histamine content of mast cell-deficient W/Wv mice using a recently developed high-performance liquid chromatography system coupled with a fluorometric detector. IP injection of (R)-alpha-methylhistamine (6-50 mg/kg) increased brain histamine content after 1 h but caused no significant change in locomotor activity. IP injection of (S)-alpha-fluoromethylhistidine decreased brain histamine content at doses of 6-50 mg/kg and locomotor activity at doses of 12.5-50 mg/kg. However, locomotor activity was decreased significantly (in Student's t-test) by sequential administrations of (S)-alpha-fluoromethylhistidine (6 mg/kg) and (R)-alpha-methylhistamine (12.5 or 25 mg/kg), but not by (S)-alpha-fluoromethylhistidine (6 mg/kg) and other doses of (R)-alpha-methylhistamine (6 or 50 mg/kg). These results support the hypothesis that the central histaminergic neuron system is involved in the control of spontaneous locomotion or alertness. |
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