Role of wake-promoting basal forebrain and adenosinergic mechanisms in sleep-promoting effects of ethanol.
Role of wake-promoting basal forebrain and adenosinergic mechanisms in sleep-promoting effects of ethanol.
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DOI：
10.1111/j.1530-0277.2010.01174.x
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发表时间：
2010-06
期刊：
影响因子：
--
通讯作者：
Sahota P
中科院分区：
文献类型：
--
作者：
Thakkar MM;Engemann SC;Sharma R;Sahota P
Ethanol intake has significant impact on sleep. However, the cellular substrates responsible for sleep promotion following ethanol intake are unknown. The purine nucleoside, adenosine, is responsible for mediating many neuronal and behavioral responses to ethanol. Studies performed in cell cultures suggest that ethanol inhibits equilibrative nucleoside transporter 1 to block the reuptake of adenosine resulting in increased extracellular adenosine. Adenosine also has a pivotal role in sleep regulation. Adenosine acts via A1 receptor to inhibit the wake-promoting neurons of the basal forebrain (BF) resulting in the promotion of sleep. Is ethanol induced sleep associated with the inhibition of the BF wake-promoting neurons? Do adenosinergic mechanisms in the BF have a role in sleep-promoting effects of ethanol? To address these questions, we performed three experiments in Sprague Dawley rats. First, we verified the effect of ethanol on sleep promotion. Second, we evaluated the effect of ethanol on c-Fos expression (a marker of neuronal activation) in the BF wake-promoting neurons and third we monitored the effects of A1 receptor blockade in the BF on ethanol induced sleep. Significant increase in non-rapid eye movement (NREM) sleep with a concomitant decrease in wakefulness was observed during first 12 hours post- ethanol. REM sleep remained unaffected. Ethanol administration caused a significant decrease in the number of BF wake-promoting neurons with c-Fos immunoreactivity. Bilateral microinjections of a selective A1R receptor antagonist 8-cyclopentyl-1, 3-dipropylxanthine into the BF significantly attenuated sleep-promoting effects of ethanol. These results suggest that the inhibition of BF wake-promoting neurons by adenosinergic mechanism may be responsible for the sleep promoting effects of ethanol. We believe our study is the first to investigate the cellular mechanisms responsible for the somnogenic effects of ethanol.
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影响因子：
3.3
作者：
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通讯作者：
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影响因子：
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DOI：
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发表时间：
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期刊：
MOLECULAR BRAIN RESEARCH
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