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Ethosuximide Reduces Ethanol Withdrawal–Mediated Disruptions in Sleep-Related EEG Patterns

Authors

  • Walter F. Wiggins,

    1. The Neuroscience Program , Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina
    2. Department of Neurobiology & Anatomy , Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina
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  • John D. Graef,

    1. The Neuroscience Program , Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina
    2. Department of Neurobiology & Anatomy , Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina
    Current affiliation:
    1. Preclinical Research, Targacept Inc., Winston-Salem, North Carolina.
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  • Tiffany W. Huitt,

    1. Department of Neurobiology & Anatomy , Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina
    Current affiliation:
    1. Department of Physical Therapy, University of Central Arkansas, Conway, Arkansas.
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  • Dwayne W. Godwin

    Corresponding author
    1. Department of Neurobiology & Anatomy , Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina
    2. Department of Physiology & Pharmacology , Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina
    • The Neuroscience Program , Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina
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  • The first two authors contributed equally to this work.

Reprint requests: Dwayne W. Godwin, PhD, Department of Neurobiology & Anatomy, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157; Tel.: 336-716-9437; Fax: 336-716-4534; E-mail: dgodwin@wakehealth.edu

Abstract

Background

Chronic ethanol (EtOH) leads to disruptions in resting electroencephalogram (EEG) activity and in sleep patterns that can persist into the withdrawal period. These disruptions have been suggested to be predictors of relapse. The thalamus is a key structure involved in both normal brain oscillations, such as sleep-related oscillations, and abnormal rhythms found in disorders such as epilepsy and Parkinson's disease. Previously, we have shown progressive changes in mouse thalamic T-type Ca2+ channels during chronic intermittent EtOH exposures that occurred in parallel with alterations in theta (4 to 8 Hz) EEG patterns.

Methods

Two groups of 8-week-old male C57BL/6 mice were implanted with wireless EEG/electromyogram (EMG) telemetry and subjected to 4 weeks of chronic, intermittent EtOH vapor exposure and withdrawal. During the week after the final withdrawal, mice were administered ethosuximide (ETX; 200 mg/kg) or saline. EEG data were analyzed via discrete Fourier transform, and sleep-scored for further analysis.

Results

Chronic intermittent EtOH exposure produced changes in the diurnal rhythms of the delta (0.5 to 4 Hz) and theta bands that persisted into a subsequent week of sustained withdrawal. These disruptions were restored with the T-channel blocker ETX. Repeated EtOH exposures preferentially increased the relative proportion of lower frequency power (delta and theta), whereas higher frequencies (8 to 24 Hz) were decreased. The EtOH-induced decreases in relative power for the higher frequencies continued into the sustained withdrawal week for both groups. Increases in absolute delta and theta power were observed in averaged nonrapid eye movement and rapid eye movement sleep spectral data during withdrawal in ETX-treated animals, suggesting increased sleep intensity.

Conclusions

These results suggest that persistent alterations in delta and theta EEG rhythms during withdrawal from chronic intermittent EtOH exposure can be ameliorated with ETX and that this treatment might also increase sleep intensity during withdrawal.

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