Chronic stress and a cyclic regimen of estradiol administration separately facilitate spatial memory: relationship with hippocampal CA1 spine density and dendritic complexity.

This study investigated the effects of chronic restraint stress and repeated cyclic estradiol pulses on hippocampal CA3 and CA1 dendritic and/or spine morphology and spatial memory in female rats. Sprague-Dawley adult female rats were ovariectomized and then injected over 2 days with 17β-estradiol (10 μg, s.c.), which was repeated every 4-5 days. While all rats received similar estradiol injection histories, half of the rats were chronically restrained and/or given a final cyclic pulse of estradiol prior to testing on a hippocampal-dependent object placement (OP) task to assess spatial memory. OP testing was performed 2 days after the last restraint session, as well as when the last 2 estradiol pulses best captured the maximal effect on hippocampal CA1 spine density. The data revealed several novel findings: (a) chronic stress or estradiol separately facilitated spatial memory, but did not have the same effects when coadministered, (b) CA1 spine densities negatively correlated with spatial memory, and (c) repeated estradiol pulses failed to prevent stress-induced CA3 dendritic retraction. We also corroborated previous studies showing increased CA1 spine density following estradiol, chronic stress, and behavioral manipulations. The present study uniquely combined chronic stress, repeated estradiol pulses, hippocampal morphology, and behavior within the same animals, allowing for correlational analyses to be performed between CA1 spine morphology and spatial memory. We demonstrate novel findings that chronic stress or estradiol pulses independently facilitate spatial memory, but not when coadministered, and that these effects may involve a balance of CA1 apical spine expression that is independent of CA3 dendritic complexity.