Eszopiclone and Zolpidem Produce Opposite Effects on Hippocampal Ripple Density

Frontiers in Pharmacology

Dara S. Manoach¹  Matthew A. Wilson²  Hector Penagos²  Francisco J. Flores³  Logan A. Becker⁸  Carmen Varela⁸ 

[1] Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States;Center for Brains Minds and Machines, Massachusetts Institute of Technology, Boston, MA, United States;Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States;Department of Neuroscience and Behavior, Stony Brook University, Stony Brook, NY, United States;Department of Neuroscience, University of Texas at Austin, Austin, TX, United States;Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States;Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, United States;Psychology Department, Florida Atlantic University, Boca Raton, FL, United States;

关键词: hippocampus;    sharp-wave ripples;    memory;    eszopiclone;    zolpidem;    sleep;   

DOI  :  10.3389/fphar.2021.792148

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown