Use of in vitro superfusion to assess the dynamics of striatal dopamine clearance: influence of estrogen

To determine the feasibility of assessing dopamine uptake using in vitro su perfusion, striatal tissue from ovariectomized female rats was infused with dopamine (1 mu M), nomifensine (1 mM), or a combination of dopamine and no mifensine. Treatment with nomifensine or dopamine/nomifensine increased the recovery of dopamine in the effluent samples as compared to treatment with dopamine alone. In Experiment 2, the striatal tissue was treated with vary ing concentrations (0, 3, 30 or 300 nM) estradiol throughout the superfusio n and subsequently given a dopamine (1 mu M) challenge. The recovery of dop amine was enhanced in the presence of 3 and 30 nM estradiol. These results show that (1) in vitro superfusion can be used to dynamically evaluate dopa mine recovery, and (2) estradiol, like nomifensine, increases the recovery of exogenously applied dopamine from the striata of ovariectomized female r ats. Such increases in dopamine recovery with estrogen and similarities to that obtained with nomifensine suggest that estrogen may be inhibiting dopa mine uptake from these striatal tissue fragments. Moreover, the doses at wh ich estrogen can exert these effects insinuates a physiological role for th is process. Our data provide a clear functional demonstration for one of th e mechanisms by which estradiol can modulate striatal dopamine neurons, tha t of an uptake inhibitor. Such a mechanism has important implications with regard to estradiol's capacity to function as a neuroprotectant of the nigr ostriatal dopaminergic system through inhibition of uptake of neurotoxins w hich can produce neurodegeneration of striatal dopamine neurons. (C) 1999 E lsevier Science B.V. All rights reserved.