Abstract
We studied the effects of inactivators of the central histaminergic neuron system, ( R)- α-methylhistamine, a histamine H 3 receptor agonist, and ( S)- α-fluoromethylhistidine, a histamine synthesis inhibitor, on locomotor activity and brain histamine content of mast cell-deficient W/ W ν mice using a recently developed high-performance liquid chromatography system coupled with a fluorometric detector. IP injection of ( R)- α-methylhistamine (6–50 mg/kg) increased brain histamine content after 1 h but caused no significant change in locomotor activity. IP injection of ( S)- α-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)- α-fluoromethylhistidine (6 mg/kg) and ( R)- α-methylhistamine (12.5 or 25 mg/kg), but not by ( S)- α-fluoromethylhistidine (6 mg/kg) and other doses of ( R)- α-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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