The Neuroscience Program, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina, USA.
Alcohol Clin Exp Res. 2013 Mar;37(3):372-82. doi: 10.1111/j.1530-0277.2012.01938.x. Epub 2012 Oct 18.
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.
慢性乙醇（EtOH）会导致静息脑电图（EEG）活动和睡眠模式的中断，这些中断在戒断期仍会持续。这些中断被认为是复发的预测因素。丘脑是一个关键的结构，涉及到正常的大脑振荡，如与睡眠相关的振荡，以及在癫痫和帕金森病等疾病中发现的异常节律。以前，我们已经显示出在慢性间歇性 EtOH 暴露期间，小鼠丘脑 T 型钙通道发生了渐进性变化，这些变化与θ（4 到 8 Hz）EEG 模式的改变平行。
两组 8 周龄雄性 C57BL/6 小鼠植入无线 EEG/肌电图（EMG）遥测仪，并接受 4 周的慢性间歇性 EtOH 蒸气暴露和戒断。在最后一次戒断后的一周内，小鼠给予乙琥胺（ETX；200mg/kg）或生理盐水。通过离散傅立叶变换分析 EEG 数据，并对睡眠进行评分以进行进一步分析。
慢性间歇性 EtOH 暴露导致 delta（0.5 到 4 Hz）和 theta 波段的昼夜节律发生变化，这些变化持续到随后的一周持续戒断期。这些中断在 T 型通道阻滞剂 ETX 的作用下得到恢复。重复的 EtOH 暴露优先增加低频功率（delta 和 theta）的相对比例，而高频（8 到 24 Hz）则降低。在两组中，EtOH 诱导的高频相对功率下降持续到持续戒断周。在 ETX 治疗的动物中，在戒断期间非快速眼动和快速眼动睡眠光谱数据的平均 delta 和 theta 功率增加，表明睡眠强度增加。
这些结果表明，慢性间歇性 EtOH 戒断期间 delta 和 theta EEG 节律的持续改变可以通过 ETX 得到改善，并且这种治疗方法也可能在戒断期间增加睡眠强度。
