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Research ArticleArticle

Reinforcing Effects of Psychostimulants in Humans Are Associated with Increases in Brain Dopamine and Occupancy of D2Receptors

Nora D. Volkow, Gene-Jack Wang, Joanna S. Fowler, Jean Logan, S. John Gatley, Cristopher Wong, Robert Hitzemann and Naomi R. Pappas
Journal of Pharmacology and Experimental Therapeutics October 1999, 291 (1) 409-415;
Nora D. Volkow
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Gene-Jack Wang
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Joanna S. Fowler
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Jean Logan
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S. John Gatley
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Cristopher Wong
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Robert Hitzemann
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Naomi R. Pappas
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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 D2receptor 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.

Footnotes

  • Send reprint requests to: Dr. Nora D. Volkow, Medical Department, Bldg. 490, Brookhaven National Laboratory, Upton, NY 11973. E-mail: volkow{at}bnl.gov

  • ↵1 This research was carried out at Brookhaven National Laboratory under support by the U.S. Department of Energy Office of Health and Environmental Research under Contract DE-ACO2–98CH10886 and by the National Institute on Drug Abuse, Grants DA09490 and DA06278.

  • Abbreviations:
    DA
    dopamine
    DAT
    dopamine transporters
    PET
    positron emission tomograph
    MP
    methylphenidate
    ST
    striatum
    CB
    cerebellum
    DV
    distribution volumes
    • Received February 23, 1999.
    • Accepted May 11, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 291 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 291, Issue 1
1 Oct 1999
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Research ArticleArticle

Reinforcing Effects of Psychostimulants in Humans Are Associated with Increases in Brain Dopamine and Occupancy of D2Receptors

Nora D. Volkow, Gene-Jack Wang, Joanna S. Fowler, Jean Logan, S. John Gatley, Cristopher Wong, Robert Hitzemann and Naomi R. Pappas
Journal of Pharmacology and Experimental Therapeutics October 1, 1999, 291 (1) 409-415;

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Research ArticleArticle

Reinforcing Effects of Psychostimulants in Humans Are Associated with Increases in Brain Dopamine and Occupancy of D2Receptors

Nora D. Volkow, Gene-Jack Wang, Joanna S. Fowler, Jean Logan, S. John Gatley, Cristopher Wong, Robert Hitzemann and Naomi R. Pappas
Journal of Pharmacology and Experimental Therapeutics October 1, 1999, 291 (1) 409-415;
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