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The mineralocorticoid receptor (MR) has a complex role in learning and memory, with excitatory effects on spatial learning in rodents. Conversely, the MR also has inhibitory effects, likely through the regulation of the hippocampal neurosteroidogenic system. This study sought to determine the influence of MR on spatial memory and on the hippocampal neurosteroidogenic system in male rats. Morris water maze was used to assess spatial learning and memory. While osmotic pumps administered MR agonists or antagonists for 14 days impaired or enhanced learning and memory, respectively, MR KO mice performed better than wild-type controls in the Morris water maze. MR KO mice were also less sensitive than wild-type mice to the disruptive effects of adrenalectomy or 17beta-estradiol. MR knockout significantly decreased the levels of neurosteroids, notably allopregnanolone, pregnenolone, and progesterone. These results suggest that MR may play a role in spatial learning and memory through modulation of hippocampal neurosteroidogenesis and that the MR may have therapeutic potential be359ba680
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