Ameliorating effects of histidine on scopolamine-induced learning deficits using an elevated plus-maze test in mice

We investigated the effects of histidine on scopolamine-induced learning deficits in the elevated plus-maze test in mice. In this test, transfer latency (TL), 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 TL on day 2 compared with that in the saline-treated group. Histidine loading (500, 800 and 1600 mg/kg) reversed the prolongation of the TL 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. However, zolantidine, a histamine H2 receptor antagonist, showed no antagonism of the effect of histidine. Thus, histamine, a decarboxylated product of histidine, elicited an ameliorating effect on scopolamine-induced learning deficit via histamine H1 receptors in mice. These findings clearly indicated that there is a close relationship between histaminergic and cholinergic systems in the brain, and that histamine may play certain important roles in learning and memory.