REINFORCING EFFECTS OF PSYCHOSTIMULANTS IN HUMANS ARE ASSOCIATED WITH INCREASES IN BRAIN DOPAMINE AND OCCUPANCY OF D2 RECEPTORS

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 [ 11 C]raclopride, a dopamine D 2 receptor radioligand that competes with endogenous dopamine for occupancy of the D 2 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 2 receptor occupancy by dopamine and the intensity of the high.