Oral administration of methylphenidate (Ritalin) affects dopamine release differentially between the prefrontal cortex and striatum: A microdialysis study in the monkey

Tohru Kodama, Takashi Kojima, Yoshiko Honda, Takayuki Hosokawa, Ken Ichiro Tsutsui, Masataka Watanabe

    Research output: Contribution to journalArticlepeer-review

    16 Citations (Scopus)

    Abstract

    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~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.

    Original languageEnglish
    Pages (from-to)2387-2394
    Number of pages8
    JournalJournal of Neuroscience
    Volume37
    Issue number9
    DOIs
    Publication statusPublished - 2017 Mar 1

    Keywords

    • Dopamine
    • Methylphenidate
    • Microdialysis
    • Monkey
    • Prefrontal cortex
    • Striatum

    ASJC Scopus subject areas

    • Neuroscience(all)

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