ERb-selective estrogen receptor modulators produce antianxiety behavior when administered systemically to ovariectomized rats

17 beta-Estradiol (E-2) may influence anxiety behavior; however, its effects and mechanisms are not well understood. To determine whether E-2's effects on anxiety behavior may involve actions at intracellular estrogen receptor (ER) alpha or beta isoforms, selective ER modulators (SERMs) were administered (10 mu g; s.c.) to ovariectomized rats 48 h before testing for anxiety behavior. Rats received sesame oil vehicle, 17 beta-E-2, which has a high affinity for ER alpha and ER beta, or SERMs that vary in their activity at ER alpha and beta. ER alpha-selective SERMs were propyl pyrazole triol (PPT), which has more selective effects at ER alpha, than does the other ER alpha SERM utilized, 17 alpha-E-2, which also binds ER beta. ER beta-selective SERMs were diarylpropionitrile (DPN) and 7,12-dihydrocoumestan (coumestrol). DPN is more selective at ERb than coumestrol, which also binds ER alpha. 17 beta-E-2 and ER beta-selective SERMs (DPN, coumestrol) produced clear antianxiety behavior in the open field, elevated plus maze, emergence, light-dark transition, defensive freezing, and Vogel punished drinking tasks. Anxiety behavior of rats administered ERa-selective SERMs (PPT, 17 alpha- E-2) was not different from vehicle; however, PPT and 17 alpha-E-2 enhanced sexual receptivity in a manner similar to 17 beta-E-2. Coadministration of tamoxifen (10 mg/kg) blocked the antianxiety behavior produced by 17 beta-E-2, DPN, or coumestrol. Together, these data suggest that actions at ER beta may underlie some of E-2's antianxiety effects.