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Methylphenidate redistributes vesicular monoamine transporter-2: role of dopamine receptors.

ABSTRACT: It is well accepted that methylphenidate (MPD) inhibits dopamine (DA) transporter function. In addition to this effect, this study demonstrates that MPD increases vesicular [3H]DA uptake and binding of the vesicular monoamine transporter-2 (VMAT-2) ligand dihydrotetrabenazine (DHTBZ) in a dose- and time-dependent manner in purified striatal vesicles prepared from treated rats. This change did not result from residual MPD introduced by the original in vivo treatment, because application of MPD in vitro (< or =1 miccrom) was without effect, and higher concentrations decreased vesicular [3H]DA uptake. In addition, MPD treatment increased and decreased VMAT-2 immunoreactivity in striatal vesicle subcellular and plasmalemmal membrane fractions, respectively. The MPD-induced increase in both VMAT-2 immunoreactivity and DHTBZ binding was attenuated by pretreatment in vivo with either the DA D(1) receptor antagonist SCH23390 or the DA D2 receptor antagonist eticlopride. Coadministration of these antagonists in vivo inhibited completely the MPD-induced increase in DHTBZ binding in the purified vesicular preparation. These observations suggest a role for DA in the MPD-induced redistribution of VMAT-2. The implications of this phenomenon will be discussed.

SUBMITTER: Sandoval V

PROVIDER: S-EPMC6757793 | biostudies-literature | 2002 Oct

REPOSITORIES: biostudies-literature

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Methylphenidate redistributes vesicular monoamine transporter-2: role of dopamine receptors.

Sandoval Verónica V Riddle Evan L EL Hanson Glen R GR Fleckenstein Annette E AE

The Journal of neuroscience : the official journal of the Society for Neuroscience 20021001 19

It is well accepted that methylphenidate (MPD) inhibits dopamine (DA) transporter function. In addition to this effect, this study demonstrates that MPD increases vesicular [3H]DA uptake and binding of the vesicular monoamine transporter-2 (VMAT-2) ligand dihydrotetrabenazine (DHTBZ) in a dose- and time-dependent manner in purified striatal vesicles prepared from treated rats. This change did not result from residual MPD introduced by the original in vivo treatment, because application of MPD in ...[more]

PMID: 12351745

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Dataset Information

Methylphenidate redistributes vesicular monoamine transporter-2: role of dopamine receptors.

Publications

Methylphenidate redistributes vesicular monoamine transporter-2: role of dopamine receptors.

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