Estrogen mediated inhibition of dopamine transport in the striatum: Regulation by Gαi/o

In the current study, the interaction between estrogen priming and dopamine D2 receptor activation on dopamine uptake in the striatum of ovariectomized female rats was investigated. Basal ADP-[32Pi]ribosylation of Gi/o was examined in synaptosomal membranes prepared from ovariectomized, estrogen primed or N-p-(isothiocyanatophenethyl) spiperone (NIPS) treated rats. [32Pi]-incorporation was significantly increased (141%) in tissue from NIPS treated animals but attenuated (57%) in tissue from estrogen primed animals. Dopamine uptake kinetics were measured in vivo following manipulation of the heterotrimeric G-protein by pertussis toxin (0.5 μg, 48 h). Pertussis toxin significantly inhibited dopamine uptake at all concentrations of dopamine examined. Co-treatment with estrogen and pertussis toxin resulted in a further attenuation of dopamine transport at high but not low dopamine concentrations. These data are consistent with an estrogen mediated alteration of G-protein activity and support the hypothesis that estrogen may alter transporter activity through a modulation of dopamine D2 autoreceptor/Gαi/o protein coupling.