Interleukin 1 receptor contributes to methamphetamine- and sleep deprivation-induced hypersomnolence.
Interleukin 1 receptor contributes to methamphetamine- and sleep deprivation-induced hypersomnolence.
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白细胞介素 1 受体会导致甲基苯丙胺和睡眠剥夺引起的嗜睡。
DOI：
10.1016/j.neulet.2012.02.040
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发表时间：
2012
影响因子：
2.5
通讯作者：
Wisor,JonathanP
中科院分区：
文献类型：
--
作者：
Schmidt,MichelleA;Wisor,JonathanP
甲基苯丙胺诱导的觉醒依赖于单胺转运体的阻断。在甲基苯丙胺诱导的觉醒之后，与基线睡眠相比，睡眠时间和睡眠深度增加。甲基苯丙胺引起睡眠过多的机制尚不完全清楚。我们最近观察到，甲基苯丙胺暴露会增加脑内CD11b阳性单核细胞中促进睡眠的细胞因子IL-1β的表达。在这里，我们试图确定白细胞介素1受体(IL1R)的激活是否会导致甲基苯丙胺诱导的觉醒后睡眠深度和睡眠时间的增加。对IL1R基因缺陷小鼠和野生型对照小鼠进行全身注射甲基苯丙胺(1 mg/kg和2 mg/kg)和生理盐水处理。甲基苯丙胺的促醒作用可因IL1R缺乏而略有增强。此外，野生型小鼠在甲基苯丙胺诱导的觉醒后，在NREMS中花费的时间增加在IL1R缺陷小鼠中被取消。在IL1R缺乏的小鼠中，行为觉醒3h后睡眠时间的增加也被消除。在IL1R缺陷小鼠和野生型小鼠中，由甲基苯丙胺和睡眠剥夺引发的脑电慢波活动的增加幅度相同。这些数据表明，IL1R的激活有助于睡眠丧失后发生的睡眠亢进，无论这种睡眠丧失是由甲基苯丙胺药物触发的，还是通过行为睡眠剥夺引发的。
Methamphetamine-induced wakefulness is dependent on monoamine transporter blockade. Subsequent to methamphetamine-induced wakefulness, the amount of time spent asleep and the depth of sleep are increased relative to baseline sleep. The mechanisms that drive methamphetamine-induced hypersomnolence are not fully understood. We recently observed that methamphetamine exposure elevates the expression of the sleep-promoting cytokine, interleukin-1β in CD11b-positive monocytes within the brain. Here, we sought to determine whether activation of the interleukin 1 receptor (IL1R) drives the increase in the depth and amount of sleep that occurs subsequent to methamphetamine-induced wakefulness. IL1R-deficient mice and wild type control mice were subjected to systemic methamphetamine (1 and 2mg/kg) and saline treatments. The wake-promoting effect of methamphetamine was modestly potentiated by IL1R-deficiency. Additionally, the increase in time spent in NREMS subsequent to methamphetamine-induced wakefulness in wild type mice was abolished in IL1R-deficient mice. The increase in time spent asleep after 3h of behaviorally enforced wakefulness was also abolished in IL1R-deficient mice. Increases in EEG slow wave activity triggered by methamphetamine and sleep deprivation were of equal magnitude in IL1R-deficient and wild type mice. These data demonstrate that IL1R activation contributes to hypersomnolence that occurs after sleep loss, whether that sleep loss is triggered pharmacologically by methamphetamine or through behavioral sleep deprivation.