Effects of (S)-alpha -fluoromethylhistidine and metoprine on locomotor activity and brain histamine content in mice.
We examined the effects of (S)-alpha -fluoromethylhistidine (FMH), an inhibitor of histidine decarboxylase, and metoprine, an inhibitor of histamine N-methyltransferase, on the locomotor activity and the brain histamine content of ICR mice. The brain histamine content was decreased by FMH (12.5 or 50 mg/kg, i.p.) and increased by metoprine (4 mg/kg, i.p.). Under these conditions, the locomotor activity and the number of rearing were significantly decreased and increased by FMH and metoprine, respectively. The higher the brain histamine content, the greater the locomotor activity and vice versa. In a previous paper [Sakai et al., Life Sciences, 48, 2397-2404 (1991)], we showed that thioperamide, a histamine H3 antagonist, which enhances the release of histamine from histaminergic neurons, in doses of 12.5 and 25 mg/kg, i.p. increases the locomotor activity, whereas it decreases the brain histamine content. Taken together, these results support the hypothesis that central histaminergic neurons may be involved in the control of state of locomotion and rearing.
Sakai
N
N
Department of Pharmacology I, School of Medicine, Tohoku University, Sendai, Japan.
Onodera
K
K
Maeyama
K
K
Yanai
K
K
Watanabe
T
T
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D006632:Histamine / Q000378:metabolism*; D006637:Histamine N-Methyltransferase / Q000037:antagonists & inhibitors*; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors*; D007274:Injections, Intraperitoneal; D008297:Male; D008762:Methylhistidines / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects*; D011739:Pyrimethamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D008762:Methylhistidines; C006308:metoprine; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D006637:Histamine N-Methyltransferase; D006640:Histidine Decarboxylase; D011739:Pyrimethamine