Estrogen priming modulates autoreceptor-mediated potentiation of dopamine uptake.

The ability of a physiological dose of estrogen (estradiol benzoate, estrogen: 10 microgram 48 and 24 h prior) to modulate autoreceptor-mediated changes in dopamine transport properties was investigated in a synaptosomal preparation prepared from the nucleus accumbens of ovariectomized rats. Quinpirole (1-100 microM)-mediated potentiation of [3H]dopamine uptake was attenuated in synaptosomes from estrogen-primed animals. Haloperidol (10 microM) inhibited basal uptake and effectively prevented quinpirole potentiation of uptake in both ovariectomized and estrogen-primed samples. The ability of selective protein phosphatase inhibitors to modulate autoreceptor-mediated potentiation of dopamine uptake was also examined. Pretreatment with protein phosphatase 2B (deltamethrin, cypermethrin) or protein phosphatase 1 (tautomycin) inhibitors attenuated basal and quinpirole-potentiated dopamine uptake in ovariectomized but not estrogen-primed tissue. These data suggest that autoreceptor-mediated activation of dopamine transport can be regulated by physiological doses of estrogen and implicate a role for protein phosphorylation in autoreceptor-mediated potentiation of dopamine uptake.