Department of Psychiatry and Human Behavior, University of California, Irvine CA 92697-4291, USA.
Pharmacol Biochem Behav. 2011 Aug;99(2):116-29. doi: 10.1016/j.pbb.2010.12.024. Epub 2011 Jan 6.
Whether drugs that enhance cognition in healthy individuals will appear in the near future has become a topic of considerable interest. We address this possibility using a three variable system (psychological effect, neurobiological mechanism, and efficiency vs. capabilities) for classifying candidates. Ritalin and modafinil, two currently available compounds, operate on primary psychological states that in turn affect cognitive operations (attention and memory), but there is little evidence that these effects translate into improvements in complex cognitive processing. A second category of potential enhancers includes agents that improve memory encoding, generally without large changes in primary psychological states. Unfortunately, there is little information on how these compounds affect cognitive performance in standard psychological tests. Recent experiments have identified a number of sites at which memory drugs could, in principle, manipulate the cell biological systems underlying the learning-related long-term potentiation (LTP) effect; this may explain the remarkable diversity of memory promoting compounds. Indeed, many of these agents are known to have positive effects on LTP. A possible third category of enhancement drugs directed specifically at integrated cognitive operations is nearly empty. From a neurobiological perspective, two plausible candidate classes have emerged that both target the fast excitatory transmission responsible for communication within cortical networks. One acts on nicotinic receptors (alpha7 and alpha4) that regulate release of the neurotransmitter glutamate while the other ('ampakines') allosterically modulates the glutamate receptors mediating the post-synaptic response (EPSCs). Brain imaging in primates has shown that ampakines expand cortical networks engaged by a complex task; coupled with behavioral data, these findings provide evidence for the possibility of generating new cognitive capabilities. Finally, we suggest that continuing advances in behavioral sciences provide new opportunities for translational work, and that discussions of the social impact of cognitive enhancers have failed to consider the distinction between effects on efficiency vs. new capabilities.
在健康个体中增强认知的药物是否会在不久的将来出现，已成为一个备受关注的话题。我们使用一个三变量系统（心理效应、神经生物学机制和效率与能力）来对候选药物进行分类，以此来探讨这种可能性。利他林和莫达非尼是两种现有的化合物，它们作用于主要的心理状态，进而影响认知操作（注意力和记忆力），但几乎没有证据表明这些效果会转化为复杂认知处理的改善。潜在增强剂的第二类包括改善记忆编码的药物，一般不会对主要心理状态产生大的影响。遗憾的是，关于这些化合物如何影响标准心理测试中的认知表现，信息很少。最近的实验已经确定了一些药物作用的靶点，这些药物原则上可以操纵学习相关的长时程增强（LTP）效应背后的细胞生物学系统；这可以解释记忆促进化合物的显著多样性。事实上，许多这些药物已知对 LTP 有积极影响。一个可能的第三类专门针对综合认知操作的增强药物几乎是空白的。从神经生物学的角度来看，已经出现了两个有希望的候选类别，它们都针对负责皮质网络内通讯的快速兴奋性传递。一种作用于烟碱受体（alpha7 和 alpha4），调节神经递质谷氨酸的释放，而另一种（“ampakines”）变构调节介导突触后反应（EPSCs）的谷氨酸受体。灵长类动物的脑成像显示，ampakines 扩展了参与复杂任务的皮质网络；与行为数据相结合，这些发现为产生新的认知能力的可能性提供了证据。最后，我们认为行为科学的持续进步为转化工作提供了新的机会，而对认知增强剂的社会影响的讨论未能考虑到效率与新能力的区别。
