Oral Administration of Methylphenidate (Ritalin) Affects Dopamine Release Differentially Between the Prefrontal Cortex and Striatum: A Microdialysis Study in the Monkey
Oral Administration of Methylphenidate (Ritalin) Affects Dopamine Release Differentially Between the Prefrontal Cortex and Striatum: A Microdialysis Study in the Monkey
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DOI：
10.1523/jneurosci.2155-16.2017
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发表时间：
2017-03-01
影响因子：
5.3
通讯作者：
Watanabe, Masataka
中科院分区：
文献类型：
--
作者：
Kodama, Tohru;Kojima, Takashi;Watanabe, Masataka
哌醋甲酯（MPH;商品名Ritalin）是一种广泛用于治疗注意力缺陷多动障碍（ADHD）的药物，并且通常用作认知增强剂。由于MPH通过阻断人纹状体中的多巴胺（DA）转运体来增加DA的释放，因此MPH应该通过纹状体中DA的增加来对注意力和认知起作用。然而，ADHD患者表现出受损的前额叶皮层（PFC）的功能和MPH管理与增加的PFC中的神经活动。虽然MPH是指增加DA释放在大鼠PFC，一直没有研究，以检查MPH诱导的DA变化在人类PFC，因为技术困难与PFC DA受体的低水平。利用微透析技术，我们研究了口服MPH对猴PFC和纹状体DA释放的影响。我们还测试了MPH对认知任务绩效的影响。在人类研究中，在纹状体中，高剂量和低剂量的MPH都诱导DA释放的一致增加，与给药后30分钟相似。在PFC中，观察到DA释放的一致增加后1小时，高剂量，但不是低剂量的MPH。低剂量的MPH改善了认知任务的表现，但高剂量的MPH使猴子昏昏欲睡。因此，低剂量MPH诱导的认知增强得到纹状体DA增加的支持。
Methylphenidate (MPH; trade name Ritalin) is a widely used drug for the treatment of attention deficit hyperactivity disorder (ADHD) and is often used as a cognitive enhancer. Because MPH increases dopamine (DA) release by blocking the DA transporter in the human striatum, MPH is supposed to work on attention and cognition through a DA increase in the striatum. However, ADHD patients show impaired prefrontal cortex (PFC) function and MPH administration is associated with increased neural activity in the PFC. Although MPH is indicated to increase DA release in the rat PFC, there has been no study to examine MPH-induced DA changes in the human PFC because of technical difficulties associated with the low level of PFC DA receptors. Using the microdialysis technique, we examined the effects of oral administration of MPH on DA release in both the PFC and striatum in the monkey. We also tested the effect of MPH on cognitive task performance. As in human studies, in the striatum, both high and low doses of MPH induced consistent increases in DA release similar to 30 min after their administrations. In the PFC, a consistent increase in DA release was observed 1 h after a high dose, but not low doses, of MPH. Low doses of MPH improved cognitive task performance, but a high dose of MPH made the monkey drowsy. Therefore, low-dose MPH-induced cognitive enhancement is supported by striatum DA increase.