Estradiol to aged female or male mice improves learning in inhibitory avoidance and water maze tasks

Abstract

Although 17β-Estradiol (E 2) improves cognitive performance of aged female mice, its mnemonic effects when administered post-training to aged male mice have not been examined. E 2 (10 μg, SC) or oil vehicle was administered to intact, 24-month-old female or male congenic (primarily C57BL/6 background) mice immediately after training in the inhibitory avoidance or water maze tasks. Following behavioral testing, effects of 1 or 24 h of E 2 exposure on hippocampal levels of E 2 and brain-derived neurotrophic factor (BDNF) were examined. Female and male mice administered E 2 showed significantly better performance in the inhibitory avoidance task than did vehicle-administered mice. When tested 24 h after training, mice that received E 2 had significantly longer latencies to cross-over to the shock-associated side of the chamber than did vehicle-administered mice. Female or male mice administered E 2 showed significantly better performance in the reference memory aspect of the spatial water maze task. When tested 30 min after training, mice administered E 2 had shorter latencies to, and spent longer swimming in, the quadrant that the hidden platform had previously been located in. E 2 administration produced physiological levels of E 2 in the hippocampus 1 and 24 h after E 2. BDNF levels in the hippocampus were decreased following 1 h of E 2 exposure compared to vehicle. These findings suggest that E 2 to female and male mice may overcome age-related deficits in reference memory in an emotional or spatial learning task.