Acute ethanol disrupts photic and serotonergic circadian clock phase-resetting in the mouse.
Acute ethanol disrupts photic and serotonergic circadian clock phase-resetting in the mouse.
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DOI：
10.1111/j.1530-0277.2011.01483.x
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发表时间：
2011-08
期刊：
影响因子：
--
通讯作者：
Glass JD
中科院分区：
文献类型：
--
作者：
Brager AJ;Ruby CL;Prosser RA;Glass JD
酗酒与昼夜节律和睡眠受损有关。乙醇给药会扰乱生物钟相位重置，这表明酒精滥用对昼夜节律系统产生破坏性影响的一种模式。在本研究中，我们将之前在 C57BL/6J 小鼠中的工作扩展到：1）表征急性全身乙醇给药的 SCN 药代动力学； 2）探索急性乙醇对光和非光相位重置的影响； 2) 确定 SCN 是否是光效应的直接目标。首先，使用微透析来表征急性腹腔注射的药代动力学。在小鼠视交叉上 (SCN) 生物钟中注射 3 剂乙醇（0.5、1.0 和 2.0 g/kg）。其次，急性腹腔注射的影响。评估了乙醇给药对昼夜节律活动节律的光相位延迟和血清素能（[+]8-OH-DPAT诱导）相位提前的影响。第三，表征了 SCN 的反向微透析乙醇灌注对光相位重置的影响。 SCN 中 3 剂乙醇的乙醇浓度峰值出现在注射后 20-40 分钟内，清除半衰期为 0.6-1.8 小时。全身乙醇治疗剂量依赖性地减弱光和血清素能相位重置。这种治疗也不影响通过 Fos 表达评估的基础 SCN 神经元活动。 SCN 内灌注乙醇显着减少了光相位延迟。这些结果证实，急性乙醇可减弱小鼠的光相延迟移和血清素能相提前移。这种双重效应可能会破坏控制生物钟计时的光和非光夹带机制。同样重要的是，SCN 时钟是乙醇对光移破坏作用的直接目标。乙醇的这种作用可能是酒精滥用对与酗酒相关的行为、生理和内分泌节律造成破坏性影响的基础。
Alcohol abuse is associated with impaired circadian rhythms and sleep. Ethanol administration disrupts circadian clock phase-resetting, suggesting a mode for the disruptive effect of alcohol abuse on the circadian timing system. In this study, we extend previous work in C57BL/6J mice to: 1) characterize the SCN pharmacokinetics of acute systemic ethanol administration; 2) explore the effects of acute ethanol on photic and non-photic phase-resetting; and 2) determine if the SCN is a direct target for photic effects. First, microdialysis was used to characterize the pharmacokinetics of acute i.p. injections of 3 doses of ethanol (0.5, 1.0 and 2.0 g/kg) in the mouse suprachiasmatic (SCN) circadian clock. Second, the effects of acute i.p. ethanol administration on photic phase-delays and serotonergic ([+]8-OH-DPAT-induced) phase-advances of the circadian activity rhythm were assessed. Third, the effects of reverse-microdialysis ethanol perfusion of the SCN on photic phase-resetting were characterized. Peak ethanol levels from the 3 doses of ethanol in the SCN occurred within 20–40 min post-injection with half-lives for clearance ranging from 0.6–1.8 hr. Systemic ethanol treatment dose-dependently attenuated photic and serotonergic phase-resetting. This treatment also did not affect basal SCN neuronal activity as assessed by Fos expression. Intra-SCN perfusion with ethanol markedly reduced photic phase-delays. These results confirm that acute ethanol attenuates photic phase-delay shifts and serotonergic phase-advance shifts in the mouse. This dual effect could disrupt photic and non-photic entrainment mechanisms governing circadian clock timing. It is also significant that the SCN clock is a direct target for disruptive effects of ethanol on photic shifting. Such actions by ethanol could underlie the disruptive effects of alcohol abuse on behavioral, physiological, and endocrine rhythms associated with alcoholism.
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影响因子：
2.9
作者：
MeyerBernstein, EL;Blanchard, JH;Morin, LP
通讯作者：
Morin, LP
影响因子：
2.9
作者：
Mistlberger, RE;Antle, MC
通讯作者：
Antle, MC
DOI：
10.1007/bf01342701
发表时间：
1988-01-01
影响因子：
2.1
作者：
MROSOVSKY, N
通讯作者：
MROSOVSKY, N
影响因子：
16.2
作者：
KORNHAUSER, JM;NELSON, DE;TAKAHASHI, JS
通讯作者：
TAKAHASHI, JS
影响因子：
2.9
作者：
Bachtell, RK;Wang, YM;Ryabinin, AE
通讯作者：
Ryabinin, AE