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Improving Effects of Huperzine A on Spatial Working Memory in Aged Monkeys and
Young Adult Monkeys with Experimental Cognitive Impairment
Jia Wei Ye,
Jing Xia Cai, Li Ming Wang and Xi Can Tang
State Key Laboratory of Drug
Research, Shanghai Institute of Materia Medica, Chinese Academy of
Sciences, Shanghai, P.R. China (J.W.Y., L.M.W., and X.C.T.); and
Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming,
Yunnan, P.R. China (J.X.C.)
0022-3565/99/2882-0814$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Our previous studies demonstrated that
huperzine A, a reversible and selective acetylcholinesterase
inhibitor, exerts beneficial effects on memory deficits
in various rodent models of amnesia. To extend the
antiamnesic action of huperzine A to nonhuman primates,
huperzine A was evaluated for its ability to reverse the deficits
in spatial memory produced by scopolamine in young adult
monkeys or those that are naturally occurring in aged
monkeys using a delayed-response task. Scopolamine, a
muscarinic receptor antagonist, dose dependently impaired
performance with the highest dose (0.03 mg/kg, i.m.)
producing a significant reduction in choice accuracy in
young adult monkeys. The delayed performance changed from an
average of 26.8/30 trials correct on saline control to an
average of 20.2/30 trials correct after scopolamine
administration. Huperzine A (0.01-0.1 mg/kg, i.m.)
significantly reversed deficits induced by scopolamine in
young adult monkeys on a delayed-response task;
performance after an optimal dose (0.1 mg/kg) averaged 25.0/30
correct. In four aged monkeys, huperzine A (0.001-0.01 mg/kg,
i.m.) significantly increased choice accuracy from 20.5/30 on
saline control to 25.2/30 at the optimal dose (0.001 mg/kg for
two monkeys and 0.01 mg/kg for the other two monkeys). The
beneficial effects of huperzine A on delayed-response
performance were long lasting; monkeys remained improved
for about 24 h after a single injection of huperzine
A. This study extended the findings that huperzine A
improves the mnemonic performance requiring working
memory in monkeys, and suggests that huperzine A may be a promising
agent for clinical therapy of cognitive impairments in
patients with Alzheimer's disease.
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