Role of dopamine in the therapeutic and reinforcing effects of methylphenidate in humans: Results from imaging studies

Nora D. Volkow, Joanna S. Fowler, Gene Jack Wang, Yu Shin Ding, Samuel J. Gatley

Research output: Contribution to journalArticlepeer-review

174 Scopus citations

Abstract

Methylphenidate is the most commonly prescribed drug for the treatment of ADHD. We have used positron emission tomography to assess the role that methylphenidate's effects in brain dopamine have on its therapeutic and reinforcing effects. We have documented that in the human brain therapeutic doses of methylphenidate block more than 50% of the dopamine transporters and significantly enhance extracellular DA, an effect that appears to be modulated by the rate of DA release. Thus, we postulate that methylphenidate's therapeutic effects are in part due to amplification of DA signals, that variability in responses is in part due to differences in DA tone and that methylphenidate's effects are context dependent. Methylphenidate-induced increases in DA are also associated with its reinforcing effects but only when this occurs rapidly, as with intravenous administration. Moreover, abuse of methylphenidate is constrained by its long half-life, which we postulate limits the frequency at which it can be administered.

Original languageEnglish
Pages (from-to)557-566
Number of pages10
JournalEuropean Neuropsychopharmacology
Volume12
Issue number6
DOIs
StatePublished - Dec 2002
Externally publishedYes

Keywords

  • Abuse
  • Cocaine
  • PET
  • Pharmacokinetics
  • Ritalin
  • Routes of Administration
  • Stimulants

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