HUPERZINE-A AMELIORATES THE SPATIAL WORKING-MEMORY IMPAIRMENTS INDUCED BY AF64A

HUPERZINE A, a novel, potent, reversible, and selective acetylcholines terase (AChE) inhibitor has been expected to be superior to other AChE inhibitors now for the treatment of memory deficits in patients with Alzheimer's disease. We have assessed the effects of huperzine A on pe rformance of AF64A-treated rats in the radial maze. AF64A (2 nmol per side, i.c.v.) caused significant impairment in rats' ability to perfor m the spatial working memory task. This behavioural impairment was ass ociated with a significant decrease in the activity of choline acetylt ransferase (ChAT) in the hippocampus. Huperzine A (0.4-0.5 mg kg(-1) i .p.) significantly ameliorated the AF64A-induced memory deficit. These results suggest that AF64A is a useful agent for disrupting working m emory processes by altering hippocampal cholinergic function, and such impairment can be effectively ameliorated by huperzine A.