Eszopiclone selectively enhances hippocampal theta synchronization compared to other GABAA receptor modulators

Eszopiclone is a non-benzodiazepine hypnotic that positively modulates GABAA receptors (GABAA-Rs). While its sedative effects are well established, its influence on hippocampal network oscillations underlying memory and cognitive processing has received limited attention. We compared eszopiclone with GABAA-R modulators having different subunit selectivity profiles: diazepam, zolpidem, etomidate, and the α5-selective inverse agonist L655,607.

Chronic electrophysiological recordings were obtained from the hippocampus of freely behaving rats. Spectral power in theta (5–10 Hz), beta (13–30 Hz), and gamma (30–50 Hz) bands and theta peak frequency and amplitude were analyzed before and after drug administration. All positive allosteric modulators (eszopiclone, diazepam, zolpidem) reduced peak theta frequency and increased beta and gamma power, whereas etomidate and L655,607 had minimal effects on these measures.

However, only eszopiclone produced a significant, dose-dependent increase in theta peak amplitude; diazepam and zolpidem did not. Thus, theta frequency slowing was shared by the GABAA-R positive modulators, whereas increased theta peak amplitude was unique to eszopiclone. This dissociation suggests that oscillation frequency and spectral organization may represent separable effects of GABAergic modulation.

The distinct effect of eszopiclone may contribute to its characteristic electrophysiological and cognitive profile. Department of Psychiatry-BIDMC, Harvard Medical School, Boston, USA The authors declare no competing interests. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Below is the link to the electronic supplementary material. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it.

The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.