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Vol. 288, Issue 1, 14-20, January 1999
Brookhaven National Laboratory, Upton, New York (N.D.V., G.J.W.,
J.S.F., S.J.G., J.L., Y.S.D., S.L.D., A.N.G., N.P.); and
Department
of Psychiatry, State University of New York at Stony Brook, Stony
Brook, New York (N.D.V., R.H.)
The reinforcing effects of cocaine and methylphenidate have been linked
to their ability to block dopamine transporters (DAT). Using positron
emission tomography (PET), we previously showed that intravenous
cocaine induced a significant level of DAT blockade, which was
associated with the intensity for self-reports of "high" in cocaine
abusers. In this study, we measured DAT occupancies after intravenous
methylphenidate and assessed whether they also were associated with the
"high". Occupation of DAT by intravenous MP was measured with PET
using [11C]cocaine, as a DAT ligand, in eight normal
control subjects tested with different methylphenidate doses. The ratio
of the distribution volume of [11C]cocaine in striatum to
that in cerebellum, which corresponds to
Bmax/Kd + 1, was
used as measure of DAT availability. In parallel, self-reports of
"high" were measured. Methylphenidate produced a dose-dependent
blockade of DAT with an estimated ED50 of 0.075 mg/kg. DAT
occupancies were significantly correlated with the "high"
(p < .03). However, four of the eight subjects, despite having significant levels of DAT blockade, did not perceive the
"high". Methylphenidate is as effective as cocaine in blocking DAT
in the human brain (cocaine ED50 = 0.13 mg/kg), and DAT
blockade, as for cocaine, was also associated with the "high".
However, the fact that there were subjects who despite significant DAT blockade did not experience the "high" suggests that DAT blockade, although necessary, is not sufficient to produce the "high".
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