The cognition-enhancing effects of psychostimulants involve direct action in the prefrontal cortex.
The cognition-enhancing effects of psychostimulants involve direct action in the prefrontal cortex.
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DOI：
10.1016/j.biopsych.2014.09.013
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发表时间：
2015-06-01
影响因子：
10.6
通讯作者：
Berridge CW
中科院分区：
文献类型：
--
作者：
Spencer RC;Devilbiss DM;Berridge CW
精神兴奋剂在治疗注意缺陷多动障碍（ADHD）方面非常有效。这些药物的临床疗效与其改善依赖于前额叶皮层（PFC）和扩展的额纹状体回路的认知能力密切相关。精神兴奋剂的促认知作用仅与低剂量有关。令人惊讶的是，尽管近80年的临床使用，神经生物学的促认知作用的精神兴奋剂最近才得到系统的研究。这项研究的结果明确表明，精神兴奋剂的认知增强作用涉及PFC中儿茶酚胺的优先升高以及随后去甲肾上腺素α2和多巴胺D1受体的激活。相比之下，虽然纹状体是一个关键的参与者在“PFC依赖”的认知，在检查，纹状体内的精神兴奋剂的行动是不足以提高认知。在适度超过临床范围的剂量下，精神兴奋剂似乎以牺牲其他PFC依赖性过程（例如工作记忆、反应抑制）为代价来改善PFC依赖性注意力过程。不同剂量PFC依赖性过程的差异调节似乎与去甲肾上腺素能α2与α1受体的差异参与有关。总的来说，这些证据表明，在低的临床相关剂量下，精神兴奋剂缺乏定义这类药物的行为和神经化学作用，而是主要作为认知增强剂（改善PFC依赖性功能）。这些信息具有潜在的重要临床意义，并与精神兴奋剂广泛临床使用的公共卫生政策相关，以及用于开发ADHD和其他与PFC失调相关的疾病的新型药物治疗。
Psychostimulants are highly effective in the treatment of attention deficit hyperactivity disorder (ADHD). The clinical efficacy of these drugs is strongly linked to their ability to improve cognition dependent on the prefrontal cortex (PFC) and extended frontostriatal circuit. The procognitive actions of psychostimulants are only associated with low doses. Surprisingly, despite nearly 80 years of clinical use, the neurobiology of the procognitive actions of psychostimulants has only recently been systematically investigated. Findings from this research unambiguously demonstrate that the cognition-enhancing effects of psychostimulants involve the preferential elevation of catecholamines in the PFC and the subsequent activation of norepinephrine α2- and dopamine D1 receptors. In contrast, while the striatum is a critical participant in ‘PFC-dependent’ cognition, where examined, psychostimulant action within the striatum is not sufficient to enhance cognition. At doses that moderately exceed the clinical range, psychostimulants appear to improve PFC-dependent attentional processes at the expense of other PFC-dependent processes (e.g. working memory, response inhibition). This differential modulation of PFC-dependent processes across dose appears to be associated with the differential involvement of noradrenergic α2 vs. α1 receptors. Collectively, this evidence indicates that at low, clinically-relevant doses, psychostimulants are devoid of the behavioral and neurochemical actions that define this class of drugs and instead act largely as cognitive enhancers (improving PFC-dependent function). This information has potentially important clinical implications as well as relevance for public health policy regarding the widespread clinical use of psychostimulants and for the development of novel pharmacological treatments for ADHD and other conditions associated with PFC dysregulation.
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影响因子：
7.6
作者：
Berridge, Craig W.
通讯作者：
Berridge, Craig W.
影响因子：
3.7
作者：
Arnsten, Amy F. T.
通讯作者：
Arnsten, Amy F. T.
DOI：
10.1073/pnas.1011975107
发表时间：
2010-09-21
影响因子：
11.1
作者：
Barsegyan, Areg;Mackenzie, Scott M.;Roozendaal, Benno
通讯作者：
Roozendaal, Benno
影响因子：
2.3
作者：
Berridge, CW;Stalnaker, TA
通讯作者：
Stalnaker, TA
影响因子：
3.1
作者：
Arnsten, AFT;Simon, F
通讯作者：
Simon, F