TY - JOUR
T1 - Oral administration of methylphenidate (Ritalin) affects dopamine release differentially between the prefrontal cortex and striatum
T2 - A microdialysis study in the monkey
AU - Kodama, Tohru
AU - Kojima, Takashi
AU - Honda, Yoshiko
AU - Hosokawa, Takayuki
AU - Tsutsui, Ken Ichiro
AU - Watanabe, Masataka
N1 - Funding Information:
This work was supported by the Ministry of Education, Culture, Sports, Science and Technology of Japan (Grantin- Aid for Scientific Research JP25280052 to T.K. and Grants JP24223004 and JP26540073 to M.W.).
Publisher Copyright:
© 2017 the authors.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - 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.
AB - 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.
KW - Dopamine
KW - Methylphenidate
KW - Microdialysis
KW - Monkey
KW - Prefrontal cortex
KW - Striatum
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U2 - 10.1523/JNEUROSCI.2155-16.2017
DO - 10.1523/JNEUROSCI.2155-16.2017
M3 - Article
C2 - 28154152
AN - SCOPUS:85014486715
VL - 37
SP - 2387
EP - 2394
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 9
ER -