Effect of huperzine A on working memory in reserpine- or yohimbine-treated monkeys

The effect of huperzine A, a reversible and selective acetylcholinesterase inhibitor, on reserpine- or yohimbine-induced spatial working memory deficits in monkeys has been examined using the delayed response task that depends on the integrity of prefrontal cortex. Reserpine (0.1 mg/kg, i.m.) or yohimbine (0.01 mg/kg, i.m.) led to significant impairments in the monkeys' ability to perform the delayed response task. Huperzine A (0.01 mg/kg, i.m. in reserpine-treated monkeys; 0.01-0.1 mg/kg, i.m. in yohimbine-treated monkeys) significantly improved the reserpine- or yohimbine-induced memory impairments. The effect of huperzine A on memory impairments exhibited an inverted U-shaped dose-response pattern. Our data suggest that huperzine A may improve working memory via an adrenergic mechanism.