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

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 B(max)/K(d), 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.