Catecholamine influences on dorsolateral prefrontal cortical networks.

Catecholamine influences on dorsolateral prefrontal cortical networks.
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DOI:
10.1016/j.biopsych.2011.01.027
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发表时间:
2011-06-15
影响因子:
10.6
通讯作者:
Arnsten, Amy F. T.
Arnsten, Amy F. T.
中科院分区:
医学1区
文献类型:
--
作者:
Arnsten, Amy F. T.

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注意缺陷/多动障碍(ADHD)的症状包括前额叶皮质自上而下对注意力和行为的调节受损。目前所有针对ADHD的药物治疗都促进儿茶酚胺的传递,基础研究表明这些化合物在前额叶皮质(PFC)有显著作用。背外侧PFC对去甲肾上腺素和多巴胺的水平特别敏感,过少或过多都会明显损害PFC的功能。近期的生理学研究表明,去甲肾上腺素通过刺激PFC神经元上的突触后α2A - 肾上腺素能受体,增强PFC网络连接性,并在工作记忆任务期间维持持续放电。相反,多巴胺作用于D1受体以缩小空间调谐,塑造网络输入以减少噪声(即稳定表征)。兴奋剂药物和托莫西汀似乎通过阻断去甲肾上腺素和/或多巴胺转运体间接增强这些儿茶酚胺的作用来提高PFC功能。相比之下,胍法辛模拟去甲肾上腺素在PFC突触后α2A - 受体的增强作用,加强网络连接性。PFC对注意力、行为和情绪更强的调节可能有助于这些药物治疗ADHD的疗效。
The symptoms of attention-deficit/hyperactivity disorder (ADHD) involve impairments in prefrontal cortical top-down regulation of attention and behavior. All current pharmacological treatments for ADHD facilitate catecholamine transmission, and basic research suggests that these compounds have prominent actions in the prefrontal cortex (PFC). The dorsolateral PFC is especially sensitive to levels of norepinephrine and dopamine, whereby either too little or too much markedly impairs PFC function. Recent physiological studies have shown that norepinephrine strengthens PFC network connectivity and maintains persistent firing during a working memory task through stimulation of postsynaptic α2A-adrenoceptors on PFC neurons. Conversely, dopamine acts at D1 receptors to narrow spatial tuning, sculpting network inputs to decrease noise (i.e., stabilization of the representation). The stimulant medications and atomoxetine appear to enhance PFC function by indirectly increasing these catecholamine actions through blockade of norepinephrine and/or dopamine transporters. In contrast, guanfacine mimics the enhancing effects of norepinephrine at postsynaptic α2A-receptors in the PFC, strengthening network connectivity. Stronger PFC regulation of attention, behavior, and emotion likely contributes to the therapeutic effects of these medications for the treatment of ADHD.
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