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Volkow, N D; Wang, G J; Fowler, J S; Gatley, S J; Logan, J; Ding, Y S; Dewey, S L; Hitzemann, R; Gifford, A N; Pappas, N R
The Journal of pharmacology and experimental therapeutics 288, Številka: 1Journal Article
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 11Ccocaine, as a DAT ligand, in eight normal control subjects tested with different methylphenidate doses. The ratio of the distribution volume of 11Ccocaine 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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