Antidepressant effects of ERβ-selective estrogen receptor modulators in the forced swim test

Abstract

Estradiol (E 2) may influence depressive symptomology of women and decrease depressive behavior among rodents. The mechanism(s) for E 2's antidepressant effects are not well understood. To determine whether antidepressant effects of E 2 may involve actions at intracellular estrogen receptor (ER) α or β isoforms, selective ER modulators (SERMs) were administered (10 μg sc) to ovariectomized rats 48 h before testing in the forced swim test, an animal model of depression, and the horizontal crossing task. Rats received sesame oil vehicle, 17β-E 2, which has a high affinity for ERα and ERβ, SERMs that vary in their activity at ERα and β, or a tricyclic antidepressant (desipramine; 30 mg/kg ip), as a positive control. ERα-selective SERMs were propyl pyrazole triol (PPT) and 17α-E 2. PPT has more selective effects at ERα than does 17α-E 2, which also binds ERβ. ERβ-selective SERMs were diarylpropionitrile (DPN) and 7,12-dihydrocoumestan (coumestrol). DPN is more selective at ERβ than coumestrol, which also binds ERα. 17β-E 2, ERβ-selective SERMs (DPN, coumestrol), and desipramine administration produced antidepressive behavior (decreased immobility, increased struggling and swimming). ERα-selective SERMs (PPT, 17α-E 2) were not different from vehicle. There were no differences among groups in the number of beam breaks made in the horizontal crossing task. These data suggest that E 2's antidepressive effects may involve actions at ERβ.