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Eszopiclone and Zolpidem Produce Opposite Effects on Hippocampal Ripple Density
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fphar-12-792148.pdf
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2.64 MB
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Checksum (MD5)
14bb3b3c13f563dbc0cf38df0129f2e8
Author(s)
Becker, Logan A.
Penagos, Hector
Flores, Francisco J.
Manoach, Dara S.
Wilson, Matthew A.
Varela, Carmen
Date Issued
January 11, 2022
Journal
Frontiers in Pharmacology
Publisher
Frontiers Media SA
Citation
Becker, Logan A., Penagos, Hector, Flores, Francisco J., Manoach, Dara S., Wilson, Matthew A. et al. 2022. "Eszopiclone and Zolpidem Produce Opposite Effects on Hippocampal Ripple Density." Frontiers in Pharmacology, 12.
Version
Final published version
Abstract
Clinical populations have memory deficits linked to sleep oscillations that can potentially be treated with sleep medications. Eszopiclone and zolpidem (two non-benzodiazepine hypnotics) both enhance sleep spindles. Zolpidem improved sleep-dependent memory consolidation in humans, but eszopiclone did not. These divergent results may reflect that the two drugs have different effects on hippocampal ripple oscillations, which correspond to the reactivation of neuronal ensembles that represent previous waking activity and contribute to memory consolidation. We used extracellular recordings in the CA1 region of rats and systemic dosing of eszopiclone and zolpidem to test the hypothesis that these two drugs differentially affect hippocampal ripples and spike activity. We report evidence that eszopiclone makes ripples sparser, while zolpidem increases ripple density. In addition, eszopiclone led to a drastic decrease in spike firing, both in putative pyramidal cells and interneurons, while zolpidem did not substantially alter spiking. These results provide an explanation of the different effects of eszopiclone and zolpidem on memory in human studies and suggest that sleep medications can be used to regulate hippocampal ripple oscillations, which are causally linked to sleep-dependent memory consolidation.
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
10.3389/fphar.2021.792148
