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Sleep-related vagotonic effect of zolpidem in rats

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Abstract

Rationale

Zolpidem is a relatively new nonbenzodiazepine sedative–hypnotic. The effects of zolpidem on autonomic functions remain unclear.

Objectives

The aim of this study was to evaluate the effects of zolpidem on sleep and related cardiac autonomic modulations as compared with triazolam in Wistar–Kyoto rats.

Methods

Continuous power spectral analyses of electroencephalogram (EEG), electromyogram, and heart rate variability were performed on freely moving rats during daytime sleep. The consciousness states were classified into active waking (AW), quiet sleep (QS), and paradoxical sleep (PS). Drugs were administered via gavage and data within 2 h were analyzed.

Results

All zolpidem (ZP3, 3 mg/kg; ZP30, 30 mg/kg) and triazolam (TZ0.075, 0.075 mg/kg; TZ0.75, 0.75 mg/kg) groups had longer accumulated QS time and averaged QS duration as compared with the vehicle control. The accumulated QS time and averaged QS duration of ZP3 were similar to those of TZ0.075. Significant suppressions of PS time were noted in all drug groups except ZP3. During QS, ZP3 and ZP30 exhibited significant increases of magnitude and percentage of EEG δ power, whereas TZ0.075 and TZ0.75 did not. Heart period and high-frequency power of heart rate variability increased significantly in ZP3 during all sleep–wake states. Both parameters, however, did not increase but even decreased in ZP30, TZ0.075, and TZ0.75.

Conclusions

Zolpidem not only caused a longer and deeper sleep but also led to an elevated cardiac vagal activity at a specific dose in the rat.

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Acknowledgements

H.Y. Chen and T.B J. Kuo contributed equally to this study. This study was supported by National Science Council (Taiwan) through grants NSC-93-2314-B-320-008 and a research grant (TCMRC-93-33A-01) from the Tzu Chi Charity Foundation. We thank Ms. Y.C. Lee for her excellent technical support.

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Authors and Affiliations

  1. Institute of Neuroscience, Tzu Chi University, Hualien, 970, Taiwan

    Hsiao Ying Chen, Terry B. J. Kuo, Fu-Zen Shaw, Ching J. Lai & Cheryl C. H. Yang

  2. Department of Pharmacy, Mackay Memorial Hospital Taitung Branch, Taitung, 950, Taiwan

    Hsiao Ying Chen

  3. Department of Neurology, Tzu Chi Buddhist General Hospital, Hualien, 970, Taiwan

    Terry B. J. Kuo

  4. Department of Physiology, Tzu Chi University, No. 701 Chung Yang Road, Section 3, Hualien, 970, Taiwan

    Terry B. J. Kuo, Fu-Zen Shaw, Ching J. Lai & Cheryl C. H. Yang

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  1. Hsiao Ying Chen
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  2. Terry B. J. Kuo
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  3. Fu-Zen Shaw
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Correspondence to Cheryl C. H. Yang.

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Chen, H.Y., Kuo, T.B.J., Shaw, FZ. et al. Sleep-related vagotonic effect of zolpidem in rats. Psychopharmacology 181, 270–279 (2005). https://doi.org/10.1007/s00213-005-2236-0

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  • DOI: https://doi.org/10.1007/s00213-005-2236-0

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