Ameliorating effects of histidine on learning deficits in an elevated plus-maze test in mice and the contribution of cholinergic neuronal systems.
We investigated the effects of histidine on scopolamine-induced learning deficits in the elevated plus-maze test in mice. In this test, transfer latency, the time mice took to move from the open arm to the enclosed arm, was used as an index of learning and memory. Intraperitoneal administration of scopolamine (0.5 mg/kg) prolonged the transfer latency on day 2 as compared with that in the saline-treated group. Histidine loading (500, 800 and 1600 mg/kg) reversed the prolongation of the transfer latency induced by scopolamine. This ameliorating effect of histidine was abolished by alpha-fluoromethylhistidine, an inhibitor of histidine decarboxylase, suggesting that histidine itself has no such ameliorating effect. Moreover, the ameliorating effect of histidine was antagonized by a histamine H1-receptor antagonist, pyrilamine, but not by zolantidine, a histamine H2-receptor antagonist. Thus, histamine, a decarboxylated product of histidine, elicited an ameliorating effect on scopolamine-induced learning deficit via histamine H1 receptors in mice. In the biochemical study, histidine significantly decreased acetylcholine (ACh) levels in the cerebral cortex and diencephalon of mice, and also significantly decreased them in the midbrain at a dose of 500 mg/kg. Histidine significantly increased and decreased levels of metabolites of noradrenaline and serotonin, respectively, in the brains of mice. Levels of dopamine and its metabolites were not very affected by histidine in the brains of mice. These findings clearly indicate that there is a close relationship between histaminergic and cholinergic system in the brain, and that histamine may play certain important roles in learning and memory.
Miyazaki
S
S
Biology Laboratory, Yamasa Corporation, Choshi, Japan.
Imaizumi
M
M
Onodera
K
K
D000109:Acetylcholine / Q000032:analysis; D000818:Animals; D006632:Histamine / Q000502:physiology*; D006639:Histidine / Q000494:pharmacology*; D007858:Learning / Q000187:drug effects*; D008297:Male; D018782:Maze Learning; D051379:Mice; D008813:Mice, Inbred ICR; D010275:Parasympathetic Nervous System / Q000502:physiology*; D012601:Scopolamine / Q000494:pharmacology
D006639:Histidine; D006632:Histamine; D012601:Scopolamine; D000109:Acetylcholine