Neuronal histamine inhibits methamphetamine-induced locomotor hyperactivity in mice

Whether central histaminergic (HAergic) neurons mediate the regulation of methamphetamine (MAMP)-induced hyperactivity was clarified. l-histidine (HIS; 500 and 1000 mg/kg i.p.) reduced the locomotor hyperactivity induced by MAMP (1 mg/kg i.p.) in mice, and the effect was significant only at 1000 mg/kg. HIS significantly elevated brain histamine (HA) levels, in both doses, whereas tele-methylhistamine (t-MH) levels were elevated only at 1000 mg/kg. Pretreatment with α-fluoromethylhistidine, a histidine decarboxylase inhibitor, suppressed both behavioral and biochemical effects of HIS. Metoprine, a HA-N-methyltransferase inhibitor, increased brain HA levels, decreased t-MH levels and suppressed the MAMP-induced locomotor hyperactivity. It is concluded that central HAergic systems may play an inhibitory role on the MAMP-induced locomotor hyperactivity.