Huperzine A ameliorates the spatial working memory impairments induced by AF64A

Huperzine A, a novel, potent, reversible, and selective acetylcholinesterase (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 performance of AF64A-treated rats in the radial maze. AF64A (2 nmol per side, i.c.v.) caused significant impairment in rats' ability to perform the spatial working memory task. This behavioural impairment was associated with a significant decrease in the activity of choline acetyltransferase (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 memory processes by altering hippocampal cholinergic function, and such impairment can be effectively ameliorated by huperzine A.