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Vol. 291, Issue 1, 409-415, October 1999
Brookhaven National Laboratory, 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 D2
receptor 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.
0022-3565/99/2911-0409$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics
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