Estradiol or Diarylpropionitrile Decrease Anxiety-Like Behavior of Wildtype, but Not Estrogen Receptor Beta Knockout, Mice

Clinical and basic studies demonstrate that estrogen (E-2)-based therapies influence anxiety and mood. but the receptor targets (e.g., alpha or beta isoform of the estrogen receptor, ER) for these effects requires further investigation. To address the specificity of E-2's anxiolytic-like effects through ER beta, anxiety, motor, and nociceptive behavior of ovariectomized, wildtype (WT), and ER beta knockout (beta ERKO) mice was examined. Mice were administered oil vehicle or ER agonists, 17 beta-E-2 (E-2, 0.1 mg/kg: similar affinity for ER alpha and ER beta), and a selective ER modulator. diarylpropionitrile (DPN; 0. 1 mg/kg; greater affinity for ER beta than ER alpha). 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 ER beta is important in modulation of anxiety-like behavior by E, in some tasks. Administration of E-2 or DPN to WT, but not beta ERKO. mice increased open field central entries. plus maze open arm time, zero maze open quadrant time, and social interaction. This pattern was neither seen in motor activity nor pain threshold measures. Thus, actions of ER beta may be important for modulating anxiety-like behavior of mice.