Prediction of reinforcing responses to psychostimulants in humans by braindopamine D-2 receptor levels

Objective: This study assessed whether brain dopamine De receptor levels, w hich show significant intersubject variability, predict reinforcing respons es to psychostimulants in humans. Method: [C-11]Raclopride and positron emi ssion tomography were used to measure D-2 receptor levels in 23 healthy men (mean age=34 years, SD=7) who had no drug abuse histories in order to asse ss if there were differences between the subjects who liked and those who d isliked the effects of intravenous methylphenidate (0.5 mg/kg). Results: Su bjects who liked the effects of methylphenidate had significantly lower De 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 D-2 levels found, the more intense were methylphenidate's unpleasant effects. Conclusions: These results provide preliminary evidence that D-2 receptor levels predict resp onse to psychostimulants in humans and that low D-2 receptors may contribut e to psychostimulant abuse by favoring pleasant response.