期刊
JOURNAL OF NEUROSCIENCE
卷 37, 期 9, 页码 2387-2394出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2155-16.2017
关键词
dopamine; methylphenidate; microdialysis; monkey; prefrontal cortex; striatum
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [JP25280052, JP24223004, JP26540073]
- Grants-in-Aid for Scientific Research [26540073, 26112009, 25280052, 26560455] Funding Source: KAKEN
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.
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