Estradiol was previously reported to increase striatal D(2) receptor density. The following experiments investigated the contribution of each estrogen receptor in estradiol modulation of D(2) receptors. Ovariectomized Sprague-Dawley rats were treated for 2 weeks with an agonist for ERalpha, 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT), an agonist for ERbeta, 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) and compared to estradiol treatment. Ovariectomy decreased D(2) agonist and antagonist striatal binding sites, specific binding was measured using [(3)H]quinpirole and [(3)H]spiperone. Estradiol prevented this decrease, while DPN but not PPT mimicked the estradiol increase of D(2) 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 [(3)H]spiperone specific binding in this area. In the olfactory tubercle, neither ovariectomy nor treatments changed D(2) receptor binding. Finally, both ovariectomy 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 ERbeta agonist treatment modulates D(2) receptors and suggest that ERbeta is involved in the estradiol modulation of D(2) receptors.