ERβ mediates the estradiol increase of D2 receptors in rat striatum and nucleus accumbens

Estradiol was previously reported to increase striatal D2 receptor density. The following experiments investigated the contribution of each estrogen receptor in estradiol modulation of D2 receptors. Ovariectomized Sprague–Dawley rats were treated for 2 weeks with an agonist for ERα, 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT), an agonist for ERβ, 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) and compared to estradiol treatment. Ovariectomy decreased D2 agonist and antagonist striatal binding sites, specific binding was measured using [3H]quinpirole and [3H]spiperone. Estradiol prevented this decrease, while DPN but not PPT mimicked the estradiol increase of D2 receptor specific binding. In the nucleus accumbens, ovariectomy decreased [3H]quinpirole specific binding in the core and left the shell unchanged. Similarly, estradiol and DPN but not PPT prevented this decrease. Neither ovariectomy nor treatments affected [3H]spiperone specific binding in this area. In the olfactory tubercle, neither ovariectomy nor treatments changed D2 receptor binding. Finally, both ovariectomy and treatments did not affect D2L, D2S mRNA and D2L/D2S ratios measured by semi-quantitative RT-PCR. The present results show, for the first time, that an ERβ agonist treatment modulates D2 receptors and suggest that ERβ is involved in the estradiol modulation of D2 receptors.