Estradiol or diarylpropionitrile administration to wild type, but not estrogen receptor beta knockout, mice enhances performance in the object recognition and object placement tasks

Cognitive processes mediated by the hippocampus and cortex are influenced by estradiol (E2); however, the mechanisms by which E2 has these effects are not entirely clear. As such, studies were conducted to begin to address the role of actions at the β form of the intracellular estrogen receptor (ERβ) for E2’s cognitive effects in adult female mice. We investigated whether E2 improved performance of wild type (WT) and ERβ knockout (βERKO) mice in tasks considered to be mediated by the cortex and hippocampus, the object recognition and object placement tasks. WT and βERKO mice were ovariectomized (ovx) and E2 (0.1 mg/kg), an ERβ 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 E2 has mnemonic effects, in part, due to its actions at ERβ, then WT mice administered E2 or DPN would have improved performance compared to vehicle WT controls, which would not be different from βERKO mice administered vehicle, E2 or DPN. Alternatively, activation of ERα (with E2, which is a ligand for both ERα and ERβ) may produce opposing effects on cognition and/or the activation of ERα and ERβ vs. either receptor isoform alone may produce a different pattern of effects. Results obtained supported the hypothesis that ERβ activation is important for mnemonic effects. Ovx WT, but not βERKO, mice administered E2 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 ERβ may be important for E2 or SERMs to enhance cognitive performance of female mice in the object recognition and placement tasks.