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Effect of methylphenidate on dopamine/DARPP signalling in adult, but not young, mice
Author(s) -
Fukui Ryuichi,
Svenningsson Per,
Matsuishi Toyojiro,
Higashi Hideho,
Nairn Angus C.,
Greengard Paul,
Nishi Akinori
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.02101.x
Subject(s) - dopamine , dopamine transporter , dopaminergic , methylphenidate , dopamine receptor d1 , phosphorylation , endocrinology , dopamine uptake inhibitors , medicine , dopamine plasma membrane transport proteins , phosphoprotein , chemistry , pharmacology , biology , psychology , biochemistry , attention deficit hyperactivity disorder , psychiatry
Methylphenidate (MPH), a dopamine uptake inhibitor, is the most commonly prescribed drug for the treatment of attention‐deficit/hyperactivity disorder (ADHD) in children. We examined the effect of MPH on dopamine‐ and cAMP‐regulated phosphoprotein, M r 32 kDa (DARPP‐32) phosphorylation at Thr34 (PKA‐site) and Thr75 (Cdk5‐site) using neostriatal slices from young (14–15‐ and 21–22‐day‐old) and adult (6–8‐week‐old) mice. MPH increased DARPP‐32 Thr34 phosphorylation and decreased Thr75 phosphorylation in slices from adult mice. The effect of MPH was blocked by a dopamine D1 antagonist, SCH23390. In slices from young mice, MPH did not affect DARPP‐32 phosphorylation. As with MPH, cocaine stimulated DARPP‐32 Thr34 phosphorylation in slices from adult, but not from young mice. In contrast, a dopamine D1 agonist, SKF81297, regulated DARPP‐32 phosphorylation comparably in slices from young and adult mice, as did methamphetamine, a dopamine releaser. The results suggest that dopamine synthesis and the dopamine transporter are functional at dopaminergic terminals in young mice. In contrast, the lack of effect of MPH in young mice is likely attributable to immature development of the machinery that regulates vesicular dopamine release.