Long-term depletion of brain histamine induced by alpha-fluoromethylhistidine increases feeding-associated locomotor activity in mice with a modulation of brain amino acid levels.
We examined the long-term effects of administration of (S)-alpha-fluoromethylhistidine (FMH), a specific inhibitor of histidine decarboxylase, on the spontaneous locomotor activity, food intake and brain contents of histamine, catecholamines, serotonin and amino acids of ICR mice. The distance of ambulation and number of rearings significantly increased from 8 to 15 h (20.00-03.00 h) after treatment with FMH (100 mg/kg, i.p.) and the 24-h food intake also increased significantly. On FMH treatment, the locomotor activity in movements of 3-15 cm/0.5 s was greater than that of control mice, whereas the number of slight movements (0-1 cm/0.5 s) decreased, suggesting that once a mouse treated with FMH is in motion, it moves a longer distance than a control mouse. We sacrificed mice 12 or 24 h after FMH treatment to measure the brain contents of histamine, monoamines and amino acids. Decrease of the brain histamine content to 35% of the control level was observed until 24 h after FMH treatment, but no significant changes in the brain catecholamine and serotonin contents were detected. However, the brain GABA content of ICR mice decreased to 85% of control 12 h after FMH treatment. Moreover, decrease of the brain GABA content after FMH treatment was greater in mast cell-deficient W/Wv mice, being 70 and 62% of the control level 12 and 24 h after treatment, respectively. The present experiments support the idea that the locomotor activity is affected by the central histaminergic system, directly and/or indirectly.
Sakai
N
N
Department of Pharmacology I, Tohoku University School of Medicine, Sendai, Japan.
Sakurai
E
E
Onodera
K
K
Sakurai
E
E
Asada
H
H
Miura
Y
Y
Watanabe
T
T
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002395:Catecholamines / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006632:Histamine / Q000378:metabolism*; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors*; D008297:Male; D008762:Methylhistidines / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000378:metabolism
D000596:Amino Acids; D002395:Catecholamines; D004791:Enzyme Inhibitors; D008762:Methylhistidines; D018377:Neurotransmitter Agents; D012701:Serotonin; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D006640:Histidine Decarboxylase