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Allopregnanolone (Allop) is a neurosteroid metabolite of progesterone. Allop modulates cognition, specifically learning and memory, but these effects are frequently confounded by its anxiolytic and sedative properties. We attempted to dissociate the anxiolytic effects of Allop from its mnemonic effects by employing a pharmacological challenge with d- amphetamine. Because previous research suggests that the effects of Allop may vary with the cognitive domain being tested, we assessed both spatial and non-spatial memory. Spatial memory was tested in a Morris Water Maze, and non-spatial object memory was tested on a novel discrimination task. Allop, alone or in combination with d-amphetamine did not have any significant effects on spatial memory. Neither Allop nor amphetamine alone affected memory of a novel object relative to controls, but the combination of the two produced a dissociation and enhanced performance. The results suggest that, depending on the type of memory being tested, the sedative effects of Allop can be dissociated from mnemonic effects by co-administering a sub-threshold dose of d-amphetamine.



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