Estradiol was previously reported to increase striatal D, receptor density. The following experiments investigated the contribution of each estrogen receptor in estradiol modulation of D, receptors. Ovariectomized Spragaue-Dawley rats were treated for 2 weeks with all agonist for ER alpha., 4,4',4"-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT), an agonist for ER beta 2.3-bis(4-hydroxyphenyl)-propionitrile (DPN) and compared to estradiol treatment. Ovariectomy decreased D, agonist and antagonist striatal binding sites, specific binding was measured using [H-3]quinpirole and [H-3]spiperone. Estradiol prevented this decrease, while DPN but not PPT mimicked the estradiol increase of D, receptor specific binding. In the nucleus accumbens, ovariectomy decreased [3 H]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 [H-3]spiperone specific binding in this area. In the olfactory tubercle, neither ovariectomy nor treatments changed D, receptor binding. Finally. both ovatiectomy and treatments did not affect D-2L, D-2S mRNA and D-2L/D-2s ratios measured by semi-quantitative RT-PCR. The present results show. for the first time, that an ER beta agonist treatment modulates D-2 receptors and suggest that ER is involved in the estradiol modulation of D-2 receptors. (c) 2005 Elsevier Ltd. All rights reserved.