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Adenosine A2A receptor mediates hypnotic effects of ethanol in mice

Authors :
Teng Fang
Xin-Hong Xu
Zhi-Li Huang
Hui Dong
Ze-Ka Chen
Wei-Min Qu
Xiang-Shan Yuan
Jiang-Fan Chen
Source :
Scientific Reports, Scientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
Publication Year :
2017
Publisher :
Nature Publishing Group UK, 2017.

Abstract

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.

Details

Language :
English
ISSN :
20452322
Volume :
7
Database :
OpenAIRE
Journal :
Scientific Reports
Accession number :
edsair.doi.dedup.....23584c34428309466ccb049bf04fdda1