PT - JOURNAL ARTICLE AU - Verónica Sandoval AU - Evan L. Riddle AU - Glen R. Hanson AU - Annette E. Fleckenstein TI - Methylphenidate Redistributes Vesicular Monoamine Transporter-2: Role of Dopamine Receptors AID - 10.1523/JNEUROSCI.22-19-08705.2002 DP - 2002 Oct 01 TA - The Journal of Neuroscience PG - 8705--8710 VI - 22 IP - 19 4099 - http://www.jneurosci.org/content/22/19/8705.short 4100 - http://www.jneurosci.org/content/22/19/8705.full SO - J. Neurosci.2002 Oct 01; 22 AB - 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 originalin vivo treatment, because application of MPD in vitro (≤1 μm) 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 D1receptor 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.