Prediction of reinforcing responses to psychostimulants in humans by brain dopamine D2 receptor levels

Am J Psychiatry. 1999 Sep;156(9):1440-3. doi: 10.1176/ajp.156.9.1440.


Objective: This study assessed whether brain dopamine D2 receptor levels, which show significant intersubject variability, predict reinforcing responses to psychostimulants in humans.

Method: [11C]Raclopride and positron emission tomography were used to measure D2 receptor levels in 23 healthy men (mean age = 34 years, SD = 7) who had no drug abuse histories in order to assess if there were differences between the subjects who liked and those who disliked the effects of intravenous methylphenidate (0.5 mg/kg).

Results: Subjects who liked the effects of methylphenidate had significantly lower D2 receptor levels (mean = 2.72 Bmax/Kd, SD = 0.3) than subjects who disliked its effects (mean = 3.16, SD = 0.3). Moreover, the higher the D2 levels found, the more intense were methylphenidate's unpleasant effects.

Conclusions: These results provide preliminary evidence that D2 receptor levels predict response to psychostimulants in humans and that low D2 receptors may contribute to psychostimulant abuse by favoring pleasant response.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Carbon Radioisotopes
  • Central Nervous System Stimulants / pharmacology*
  • Corpus Striatum / chemistry*
  • Corpus Striatum / diagnostic imaging*
  • Corpus Striatum / drug effects
  • Dopamine Antagonists
  • Humans
  • Male
  • Methylphenidate / pharmacology*
  • Raclopride
  • Receptors, Dopamine D2 / analysis*
  • Receptors, Dopamine D2 / drug effects
  • Reinforcement, Psychology*
  • Reward
  • Salicylamides
  • Substance-Related Disorders / etiology
  • Substance-Related Disorders / psychology
  • Tomography, Emission-Computed


  • Carbon Radioisotopes
  • Central Nervous System Stimulants
  • Dopamine Antagonists
  • Receptors, Dopamine D2
  • Salicylamides
  • Methylphenidate
  • Raclopride