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Research ArticleArticle

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
Journal of Pharmacology and Experimental Therapeutics February 1999, 288 (2) 814-819;
Jia Wei Ye
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Jing Xia Cai
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Li Ming Wang
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Xi Can Tang
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Abstract

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.

Footnotes

  • Send reprint requests to: Dr. Xi Can Tang, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 294 Tai Yuan Road, Shanghai 200031, P.R. China.

  • Abbreviations:
    AD
    Alzheimer’s disease
    ChEI
    cholinesterase inhibitor
    ChAT
    choline acetyltransferase
    NE
    norepinephrine
    DA
    dopamine
    PFC
    prefrontal cortex
    1-ANOVA-R
    one-way analysis of variance with repeated measures
    • Received May 18, 1998.
    • Accepted September 3, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 288 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 288, Issue 2
1 Feb 1999
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Research ArticleArticle

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
Journal of Pharmacology and Experimental Therapeutics February 1, 1999, 288 (2) 814-819;

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Research ArticleArticle

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
Journal of Pharmacology and Experimental Therapeutics February 1, 1999, 288 (2) 814-819;
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