Depletion of brain histamine induced by alpha-fluoromethylhistidine enhances radial maze performance in rats with modulation of brain amino acid levels.
We examined the effects of repeated administration of (S)-alpha-fluoromethylhistidine (FMH), a specific inhibitor of histidine decarboxylase (HDC), on radial maze performance and brain contents of histamine and amino acids in rats. By daily subcutaneous (s.c.) administration of FMH (100 mg/kg), rats showed significant enhancement of a radial maze performance without changes in locomotion. Six days after FMH treatment, the histamine levels both in the cerebral cortex and diencephalon decreased significantly. However, the glutamate and glycine levels significantly increased in the cerebral cortex and hippocampus. These results suggest that FMH enhances the acquisition phase of radial maze study with the increases in glutamate and glycine levels in the cerebral cortex and hippocampus of rats.
Sakai
N
N
Department of Pharmacology I, Tohoku University School of Medicine, Sendai, Japan.
Sakurai
E
E
Sakurai
E
E
Yanai
K
K
Mirua
Y
Y
Watanabe
T
T
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006632:Histamine / Q000378:metabolism*; D006633:Histamine Antagonists / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects; D008762:Methylhistidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000596:Amino Acids; D004791:Enzyme Inhibitors; D006633:Histamine Antagonists; D008762:Methylhistidines; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D006640:Histidine Decarboxylase