Sex Differences in Effects of Long-term Alprazolam use on Spatial Learning and Working and Long-term Memory in Rats
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Issue Date
2025-03-31
Authors
Williams, Julia
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Bertholomey, Megan L.
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French, Lauren
Keywords
alprazolam , benzodiazepines , consolidation , episodic memory , long-term memory , long-term use of benzodiazepines , radial arm maze , retrieval , reversal learning , sex-differences , spatial memory , working memory , xanax , acquisition , explicit memory , memory impairments , cognitive flexibility
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Abstract
Benzodiazepines are one of the most widely prescribed classes of drugs in the United States; however, the long-term use of these medications—use extending past 3 months—has multiple concerns, one being memory deficits, usually in long-term episodic memory. These impairments have been severely understudied in females, despite being a potentially vulnerable group. In the present research, male and female adult Sprague-Dawley rats were exposed to long-term administration of alprazolam. Working memory, long-term memory, and reversal learning were examined using the radial arm maze apparatus. Memory deficits were examined over the course of three test days, one directly following alprazolam cessation, one two weeks later, and one following reversal training. Results indicate a main effect of alprazolam on working memory, a main effect of alprazolam and an interaction between alprazolam and sex on long-term memory (all p < .001), and no difference in cognitive flexibility or reversal learning. These effects did not persist long-term following cessation of use. This study supports the growing body of research demonstrating deficits in memory following long-term use of benzodiazepines, while implicating an important sex-difference that should be considered. Patients, especially females, should exercise increased caution when taking these medications.
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Neuroscience
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Psychology
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Neuroscience
Psychology
Psychology
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Neuroscience, 2025
Psychology, 2025
Psychology, 2025