Methamphetamineによるマウスの運動量増加に対するL-histidineの拮抗作用に関する研究

The mechanism by which L-histidine inhibits the methamphetamine (MAP)-induced hyperactivity was examined in mice. L-histidine (1g/kg, i. p.) significantly reduced the locomotor hyperactivity induced by MAP (1mg/kg, i. p.) in either experiment using Open field or Animex apparatus, although L-histidine did not affect the locomotor activity of control mice. L-histidine elevated brain levels of histamine and tele-methylhistamine. Pretreatment with α-fluoromethylhistidine, a histidine decarboxylase inhibitor, suppressed both behavioral and biochemical effects of L-histidine. Metoprine, a histamine-N-methyltransferase inhibitor, increased brain histamine level and suppressed the MAP-induced locomotor hyperactivity. Although L-histidine (1g/kg) markedly changed brain tyrosine levels, this amino acid alone had no significant influence on the monoamine metabolism. It did not modify the change in the monoamine metabolism induced by MAP (1mg/kg), either. The inhibition by L-histidine of the MAP-induced hyperactivity was observed in the mice pretreated with para-chlorphenylalanine or atropine. These results suggest that central histaminergic systems may have an inhibitory influence on the MAP-induced locomotor hyperactivity. However, serotonergic and cholinergic mechanisms seem not to be involved in this phenomenon.