Ethosuximide reduces ethanol withdrawal-mediated disruptions in sleep-related EEG patterns

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 Ca channels during chronic intermittent EtOH exposures that occurred in parallel with alterations in theta (4 to 8 Hz) EEG patterns.

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.

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.

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.