Estradiol or diarylpropionitrile administration to wild type, but not estrogen receptor beta knockout, mice enhances...

Cognitive processes mediated by the hippocampus and cortex are influenced by estradiol (E(2)); however, the mechanisms by which E(2) has these effects are not entirely clear. As such, studies were conducted to begin to address the role of actions at the beta form of the intracellular estrogen receptor (ERbeta) for E(2)'s cognitive effects in adult female mice. We investigated whether E(2) improved performance of wild type (WT) and ERbeta knockout (betaERKO) mice in tasks considered to be mediated by the cortex and hippocampus, the object recognition and object placement tasks. WT and betaERKO mice were ovariectomized (ovx) and E(2) (0.1 mg/kg), an ERbeta selective ER modulator (SERM), diarylpropionitrile (DPN; 0.1 mg/kg), or oil vehicle was administered to mice following training in these tasks. We hypothesized that if E(2) has mnemonic effects, in part, due to its actions at ERbeta, then WT mice administered E(2) or DPN would have improved performance compared to vehicle WT controls, which would not be different from betaERKO mice administered vehicle, E(2) or DPN. Alternatively, activation of ERalpha (with E(2), which is a ligand for both ERalpha and ERbeta) may produce opposing effects on cognition and/or the activation of ERalpha and ERbeta vs. either receptor isoform alone may produce a different pattern of effects. Results obtained supported the hypothesis that ERbeta activation is important for mnemonic effects. Ovx WT, but not betaERKO, mice administered E(2) or DPN had a greater percentage of time exploring a novel object in the object recognition task and a displaced object in the object placement task. Thus, actions at ERbeta may be important for E(2) or SERMs to enhance cognitive performance of female mice in the object recognition and placement tasks.