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 (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 P form of the intracellular estrogen receptor (ER beta) for E-2'S cognitive effects in adult female mice. We investigated whether E-2 improved performance of wild type (WT) and ER beta knockout (beta ERKO) mice in tasks considered to be mediated by the cortex and hippocampus, the object recognition and object placement tasks. WT and beta ERKO mice were ovariectomized (ovx) and E-2 (0.1 mg/kg), an ER beta 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 ER beta, then WT mice administered E-2 or DPN would have improved performance compared to vehicle WT controls, which would not be different from beta ERKO mice administered vehicle, E-2 or DPN. Alternatively, activation of ER alpha (with E-2, which is a ligand for both ER alpha and ER beta) may produce opposing effects on cognition and/or the activation of ER alpha and ER beta vs. either receptor isoform alone may produce a different pattern of effects. Results obtained supported the hypothesis that ER beta activation is important for mnemonic effects. Ovx WT, but not beta ERKO, 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 ER beta may be important for E-2 or SERMs to enhance cognitive performance of female mice in the object recognition and placement tasks. (C) 2008 Elsevier Inc. All rights reserved.