Estradiol or diarylpropionitrile decrease anxiety-like behavior of wildtype but not estrogen receptor beta knockout mice

摘要

Clinical and basic studies demonstrate that estrogen (E2)-based therapies influence anxiety and mood, but the receptor targets (e.g. α or β isoform of the estrogen receptor, ER) for these effects requires further investigation. To address the specificity of E2’s anxiolytic-like effects through ERβ, anxiety, motor, and nociceptive behavior of ovariectomized, wildtype (WT) and ERβ knockout (βERKO) mice was examined. Mice were administered oil vehicle or ER agonists, 17β-E2 (E2; 0.1 mg/kg; similar affinity for ERα and ERβ), and a selective estrogen receptor modulator, diarylpropionitrile (DPN; 0.1 mg/kg; greater affinity for ERβ than ERα). Performance of mice in anxiety (open field, elevated plus maze, elevated zero maze, social interaction), motor activity (activity monitor) and nociception (tailflick, pawlick) measures was compared. Results supported our hypothesis that ERβ is important in modulation of anxiety-like behavior by E2 in some tasks. Administration of E2 or DPN to WT, but not βERKO, mice increased open field central entries, plus maze open arm time, zero maze open quadrant time, social interaction. This pattern was neither seen in motor activity nor pain threshold measures. Thus, actions of ERβ may be important for modulating anxiety-like behavior of mice.