Modulation of dopamine uptake in rat nucleus accumbens: effect of specific dopamine receptor antagonists and sigma ligands.

The ability of dopamine (DA) antagonists and sigma receptor ligands to alter [(3)H]-DA uptake was examined using synaptosomes prepared from the nucleus accumbens of female rats. Pre-incubation with compounds having a high affinity for sigma (rimcazole, haloperidol, and spiperone) receptors produced dose dependent inhibition of (3)H-DA uptake. Sulpiride, a pure DA D(2) antagonist had no effect. In contrast, DA uptake was potentiated in response to (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine, a mixed sigma receptor antagonist and DA D(2) receptor agonist. Similarly, SKF-10,047, a selective sigma receptor agonist, and progesterone, a putative endogenous ligand for the sigma receptor, produced significant increases in (3)[H]-DA uptake. These data suggest a potential role for sigma and DA ligands in the regulation of DA uptake in the nucleus accumbens.