Reinforcing effects of psychostimulants in humans are associated with increases in brain dopamine and occupancy of D2 receptors

Nora D. Volkow, Gene Jack Wang, Joanna S. Fowler, Jean Logan, S. John Gatley, Cristopher Wong, Robert Hitzemann, Naomi R. Pappas

Research output: Contribution to journalArticle

321 Scopus citations

Abstract

Increases in dopamine concentration in limbic brain regions have been postulated to underlie the reinforcing effects of psychostimulant drugs in laboratory animals. However, neither the qualitative nor the quantitative relationship between drug-induced increases in brain dopamine and the reinforcing effects of psychostimulant drugs have been investigated in humans. Positron emission tomograph and [11C]raclopride, a dopamine D2 receptor radioligand that competes with endogenous dopamine for occupancy of the D2 receptors, were used to measure changes in brain dopamine after different doses of i.v. methylphenidate in 14 healthy controls. In parallel, measures for self-reports of drug effects were obtained to assess their relationship to methylphenidate-induced changes in brain dopamine. The intensity of the 'high' induced by methylphenidate was significantly correlated with the levels of released dopamine (r = 0.78, p < .001); subjects having the greatest increases were those who perceived the most intense high. This relationship remained significant after partialing out for dose and concentration of methylphenidate in plasma. Furthermore, subjects for whom methylphenidate did not increase dopamine did not perceive a high. These results represent the first clear demonstration that stimulant-induced high, a mood descriptor that reflects reinforcing effects of drugs in humans, is associated with increases in brain dopamine, and also that there is a quantitative relationship between levels of D2 receptor occupancy by dopamine and the intensity of the high.

Original languageEnglish (US)
Pages (from-to)409-415
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume291
Issue number1
StatePublished - Oct 1 1999

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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