Abstract

The vesicular monoamine transporter-2 is the sole transporter responsible for sequestration of monoamines, including dopamine (DA), into synaptic vesicles. Previous studies demonstrate that agents that inhibit DA transporter function, such as cocaine, increase vesicular [³H]DA uptake and binding of the ligand [³H]dihydrotetrabenazine ([³H]DHTBZ), as assessed in vesicles prepared from treated rats. The present studies examine the role of DA receptors in these cocaine-induced effects. Results demonstrate that administration of the D₂ DA receptor antagonist, eticlopride, but not the D₁ DA receptor antagonist, SCH23390, inhibited these cocaine-induced increases. Similar to the effects of cocaine, treatment with the D₂ agonist, quinpirole, increased both vesicular [³H]DA uptake and [³H]DHTBZ binding. In contrast, administration of the D₁ agonist, SKF81297, was without effect on vesicular [³H]DA uptake or [³H]DHTBZ binding. Finally, coadministration of quinpirole and cocaine did not further increase vesicular [³H]DA uptake or [³H]DHTBZ binding when compared with treatment with either agent alone. These data suggest that cocaine-induced increases in vesicular DA uptake and DHTBZ binding are mediated by a D₂ receptor-mediated pathway. Furthermore, results indicate that D₂ receptor activation, per se, is sufficient to increase vesicular DA uptake.