Graduate Program in Neuroscience, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Pharmacol Biochem Behav. 2021 Jun;205:173188. doi: 10.1016/j.pbb.2021.173188. Epub 2021 Apr 9.
Clinical studies suggest that sleep impairment is a barrier to successful treatment in alcohol use disorder (AUD) patients, with sleep disruption associated with relapse to alcohol taking. To date, no preclinical study has evaluated the relationship between impaired sleep and alcohol relapse. In the present study, we used a self-administration model to investigate the effects of sleep restriction on reinstatement induced by alcohol-paired environmental cues. Using a sucrose fading protocol, male Wistar rats (N = 8) were trained to self-administer alcohol under a fixed-ratio 2 schedule of alcohol delivery such that completion of every second response resulted in the delivery of the alcohol solution and activation of the alcohol-paired cue light. Once self-administration was stable, behavior was extinguished by omitting delivery of the alcohol solution and the alcohol-paired cues. When responding reached low, stable levels, alcohol seeking was induced by re-presentation of the alcohol-paired cues but with no alcohol solution available for self-administration. To evaluate the effects of sleep restriction on cue-induced alcohol seeking, reinstatement tests were conducted after 6-h of total (slow wave + rapid eye movement [REM]) sleep restriction using the gentle handling method or after 6-h of REM sleep-only restriction using the flower pot method. Relevant control conditions also were evaluated. The results showed that acute restriction of total sleep, but not REM sleep primarily, significantly augmented cue-induced reinstatement of alcohol seeking. This increase was specific to total sleep restriction conditions and cannot be attributed to differences in alcohol intake, responding, or days to extinction. Our findings imply that acute slow wave sleep restriction is necessary and/or sufficient for the enhancement of cue-induced alcohol seeking and, further, suggest that decreased slow wave sleep in AUD patients places individuals at a unique risk for relapse.
临床研究表明，睡眠障碍是酒精使用障碍（AUD）患者治疗成功的障碍，睡眠中断与酒精复饮有关。迄今为止，尚无临床前研究评估睡眠障碍与酒精复饮之间的关系。在本研究中，我们使用自我给药模型来研究睡眠限制对酒精配对环境线索诱发复饮的影响。使用蔗糖消退方案，雄性 Wistar 大鼠（N=8）在固定比率 2 方案下接受酒精自我给药训练，即完成每两个反应就会输送酒精溶液并激活酒精配对的线索灯。一旦自我给药稳定，通过省略输送酒精溶液和酒精配对线索来使行为消退。当反应达到低而稳定的水平时，通过重新呈现酒精配对线索但没有酒精溶液可供自我给药来诱导酒精寻求。为了评估睡眠限制对线索诱导的酒精寻求的影响，在使用温和处理方法进行总共（慢波+快速眼动[REM]）6 小时睡眠限制或使用花盆方法进行仅 REM 睡眠限制 6 小时后进行再巩固测试。还评估了相关的对照条件。结果表明，急性总睡眠时间限制，而不是 REM 睡眠限制，主要显著增强了线索诱导的酒精寻求再巩固。这种增加是总睡眠限制条件特有的，不能归因于酒精摄入量、反应或消退天数的差异。我们的发现表明，急性慢波睡眠限制是增强线索诱导的酒精寻求所必需的和/或充分的，并且进一步表明 AUD 患者慢波睡眠减少使个体处于独特的复饮风险之中。
