Effect of histamine H3-receptor antagonist clobenpropit on spatial memory of radial maze performance in rats.

The effect of histamine H3-receptor antagonist, clobenpropit (VUF9153) on spatial memory deficits induced by scopolamine was investigated in rats. Eight-Arm radial maze performance was used to measure spatial memory in rats, and the brain regions were subsequently dissected and histamine contents were determined by HPLC. Intracerebroventricular (icv) injection of clobenpropit (50 micrograms) ameliorated memory impairment induced by scopolamine in both parameters of radial maze performance. The amelioration induced by clobenpropit was antagonized by an H3-agonist, (R)-alpha-methylhistamine (5-10 micrograms). alpha-Fluoromethylhistidine (10, 20 micrograms), a histidine decarboxylase inhibitor, also effectively reversed clobenpropit-induced ameliorating effects. The brain histamine H3-receptor antagonists are highly related to the spatial memory, and this action may be due to cholinergic neurons.