Adenosine A(2A) receptor mediates hypnotic effects of ethanol in mice.

Adenosine A(2A) receptor mediates hypnotic effects of ethanol in mice.
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腺苷A(2A)受体介导乙醇对小鼠的催眠作用

DOI:
10.1038/s41598-017-12689-6
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发表时间:
2017-10-04
期刊:
影响因子:
4.6
通讯作者:
Huang ZL
Huang ZL
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Fang T;Dong H;Xu XH;Yuan XS;Chen ZK;Chen JF;Qu WM;Huang ZL

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乙醇对睡眠和白天的警觉性有广泛的影响,导致过早残疾和死亡。腺苷作为一种强有力的睡眠促进物质,参与了对乙醇的许多细胞和行为反应。然而,乙醇催眠作用的机制尚不清楚。在这项研究中,我们研究了腺苷在乙醇诱导的睡眠中的作用,使用C57 BL/6Slac小鼠,腺苷A2 A受体(A2 AR)基因敲除小鼠,和他们的野生型同窝仔。结果表明,21:00腹腔注射乙醇(3.0g/kg)可使非快速眼动睡眠(NREM)潜伏期缩短,NREM睡眠持续时间延长5 h。乙醇剂量依赖性地增加NREM睡眠,这与C57 BL/6Slac小鼠与其自身对照组相比觉醒减少一致。咖啡因(5、10或15 mg/kg)是一种非特异性腺苷受体拮抗剂,在乙醇注射前30分钟(但不是之后)给药时,高剂量咖啡因(5、10或15 mg/kg)呈剂量依赖性地完全阻断乙醇诱导的NREM睡眠。此外,与野生型小鼠相比,乙醇诱导的NREM睡眠在A2 AR敲除小鼠中完全消除。这些结果强烈地表明,A2 AR是乙醇催眠作用的关键受体,并且咖啡因预处理可能是对抗乙醇催眠作用的策略。
Ethanol has extensive effects on sleep and daytime alertness, causing premature disability and death. Adenosine, as a potent sleep-promoting substance, is involved in many cellular and behavioral responses to ethanol. However, the mechanisms of hypnotic effects of ethanol remain unclear. In this study, we investigated the role of adenosine in ethanol-induced sleep using C57BL/6Slac mice, adenosine A2A receptor (A2AR) knockout mice, and their wild-type littermates. The results showed that intraperitoneal injection of ethanol (3.0 g/kg) at 21:00 decreased the latency to non-rapid eye movement (NREM) sleep and increased the duration of NREM sleep for 5 h. Ethanol dose-dependently increased NREM sleep, which was consistent with decreases in wakefulness in C57BL/6Slac mice compared with their own control. Caffeine (5, 10, or 15 mg/kg), a nonspecific adenosine receptor antagonist, dose-dependently and at high doses completely blocked ethanol-induced NREM sleep when administered 30 min prior to (but not after) ethanol injection. Moreover, ethanol-induced NREM sleep was completely abolished in A2AR knockout mice compared with wild-type mice. These findings strongly indicate that A2AR is a key receptor for the hypnotic effects of ethanol, and pretreatment of caffeine might be a strategy to counter the hypnotic effects of ethanol.
DOI: 10.1111/j.1742-7843.2004.pto950509.x
发表时间: 2004-12-01
影响因子: 3.1
作者:
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期刊: BRAIN RESEARCH
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DOI: 10.1016/s0028-3908(03)00254-5
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期刊: NEUROPHARMACOLOGY
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