Dopamine receptor reappearance after irreversible receptor blockade: effect of chronic estradiol treatment of ovariectomized rats.

It is well established that estrogen modulates central dopamine functions; however, the mechanism of this interaction is still poorly understood. We have used peripheral N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) administration to induce irreversible blockade of dopamine receptors in ovariectomized female rats, which were pretreated with estradiol (10 micrograms, twice each day for 2 weeks) or its vehicle, in order to investigate the effect of estradiol on dopamine receptor repopulation kinetics. As previously observed, chronic estradiol treatment increased both striatal D1 and D2 dopamine receptor densities and left affinities unchanged. Anterior pituitary D2 dopamine receptor density remained unchanged. One day after EEDQ administration, a similar decrease (80%) of [3H]SCH 23390 and [3H]spiperone binding to striatum of estradiol- and vehicle-treated animals was observed. Anterior pituitary D2 dopamine receptor specific binding was reduced by about 50% the day after EEDQ. Recovery after EEDQ administration showed that both receptor production rate and degradation rate constants of anterior pituitary D2 and striatal D1 receptors were slowed after chronic estradiol treatment, whereas recovery rates for striatal D2 dopamine receptors were unaffected. EEDQ administration in vehicle-treated rats did not significantly affect plasma prolactin levels, whereas the combination of estradiol pretreatment and EEDQ administration led to increased plasma prolactin levels, compared with estradiol-treated animals that did not receive EEDQ. This suggests that only a fraction of anterior pituitary dopamine receptors are required for a maximal inhibition of prolactin secretion. Estradiol affected both striatal D1 and D2 dopamine receptor densities but only D1 dopamine receptor repopulation kinetics, suggesting that it may act by different mechanisms on each dopamine receptor. Alternatively, estradiol may affect dopamine receptor interaction. Thus, the present study raises the possibility that a biochemical D1/D2 receptor interaction affects dopamine receptor biosynthesis, turnover, and/or gene expression and that estradiol may influence this dopamine receptor interaction in the striatum.