Low Doses of 17β-Estradiol Rapidly Improve Learning and Increase Hippocampal Dendritic Spines

While a great deal of research has been performed on the long-term genomic actions of estrogens, their rapid effects and implications for learning and memory are less well characterized. The often conflicting results of estrogenic effects on learning and memory may be due to complex and little understood interactions between genomic and rapid effects. Here, we investigated the effects of low, physiologically relevant, doses of 17 beta-estradiol on three different learning paradigms that assess social and non-social aspects of recognition memory and spatial memory, during a transcription independent period of memory maintenance. Ovariectomized female CD I mice were subcutaneously administered vehicle, 1.5 mu g/kg, 2 mu g/kg, or 3 mu g/kg of 17 beta-estradiol 15 minutes before social recognition, object recognition, or object placement learning. These paradigms were designed to allow the testing of learning effects within 40 min of hormone administration. In addition, using a different set of ovariectomized mice, we examined the rapid effects of 1.5 mu g/kg, 2 mu g/kg, or 3 mu g/kg of 17 beta-estradiol on CA I hippocampal dendritic spines. All 17 beta-estradiol doses tested impacted learning, memory, and CA 1 hippocampal spines. 17 beta-Estradiol improved both social and object recognition, and may facilitate object placement learning and memory. In addition, 17 beta-estradiol increased dendritic spine density in the stratum radiatum subregion of the CA I hippocampus, but did not affect dendritic spines in the lacunosum-moleculare, within 40 min of administration. These results demonstrate that the rapid actions of 17 beta-estradiol have important implications for general learning and memory processes that are not specific for a particular type of learning paradigm. These effects may be mediated by the rapid formation of new dendrite spines in the hippocampus. Neuropsychopharmacology (2012) 37, 2299-2309; doi:10.1038/npp.2012.82; published online 6 June 2012