The effect of α-2 adrenergic agonists on memory and cognitive flexibility
The effect of α-2 adrenergic agonists on memory and cognitive flexibility
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DOI：
10.1097/01.wnn.0000213919.95266.0d
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发表时间：
2006-12-01
影响因子：
1.4
通讯作者：
Beversdorf, David Q.
中科院分区：
文献类型：
--
作者：
Choi, Youngjee;Novak, John C.;Beversdorf, David Q.
背景资料：在使用β-肾上腺素能拮抗剂的研究中，去甲肾上腺素能系统调节认知灵活性，以解决基于洞察力的问题，β-肾上腺素能拮抗剂在突触后阻断去甲肾上腺素能神经传递。然而，目前还不清楚通过突触前抑制降低去甲肾上腺素能神经传递的α 2-肾上腺素能激动剂是否具有相同的效果。目的：因此，我们希望测试α 2-肾上腺素能激动剂是否对认知灵活性具有类似的效果。对18名正常成年人服用可乐定后进行认知灵活性、问题解决、言语和空间记忆任务测试（0.1mg），α（2）-激动剂，安慰剂，或麻黄碱（25 mg），去甲肾上腺素能兴奋剂。可乐定对记忆力也没有显著影响。结论：因此，α（2）-受体激动剂不会像P-受体拮抗剂那样以同样的方式影响认知灵活性。基于灵长类动物研究表明可乐定对工作记忆有益，预期可乐定对记忆的作用更好。在我们的研究中，对于常用的临床记忆任务没有观察到这种益处。这可能暗示了为什么可乐定没有表现出对认知障碍如阿尔茨海默病的疗效，尽管它在动物模型中对工作记忆有好处。
Background: The noradrenergic system modulates cognitive flexibility for insight-based problem solving in studies using beta-adrenergic antagonists, which block noradrenergic neurotransmission postsynaptically. However, it is not known whether alpha(2)-adrenergic agonists, that decrease noradrenergic neurotransmission by presynaptic inhibition, have the same effect.Objectives: Therefore, we wished to test whether alpha 2-adrenergic agonists would have a similar effect on cognitive flexibility.Methods: Eighteen normal adults were tested on cognitive flexibility, problem solving, verbal and spatial memory tasks after receiving clonidine (0.1mg), an alpha(2)-agonist, placebo, or ephedrine (25mg), a noradrenergic stimulant.Results: Three-way analysis of variance revealed no significant drug effect on cognitive flexibility or problem solving. There was also no significant effect of clonidine on memory.Conclusions: Therefore, alpha(2)-agonists do not influence cognitive flexibility in the same manner as P-antagonists. Better performance on memory with clonidine might be expected based on primate studies demonstrating benefits in working memory using clonidine. This benefit was not observed for the commonly used clinical memory tasks in our study. This may have implications for why clonidine has not demonstrated efficacy for cognitive disorders such as Alzheimer disease, despite its known benefit for working memory in animal models.