Role of adenosine and wake-promoting basal forebrain in insomnia and associated sleep disruptions caused by ethanol dependence.

Role of adenosine and wake-promoting basal forebrain in insomnia and associated sleep disruptions caused by ethanol dependence.
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DOI:
10.1111/j.1471-4159.2010.06980.x
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发表时间:
2010-11
影响因子:
4.7
通讯作者:
Thakkar MM
Thakkar MM
中科院分区:
医学2区
文献类型:
--
作者:
Sharma R;Engemann S;Sahota P;Thakkar MM

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Insomnia is a severe symptom of alcohol withdrawal; however, the underlying neuronal mechanism is yet unknown. We hypothesized that chronic ethanol exposure will impair BF adenosinergic mechanism resulting in insomnia-like symptoms. We performed a series of experiments in Sprague-Dawley rats to test our hypothesis. We used Majchrowicz’s chronic binge ethanol protocol to induce ethanol dependency. Our first experiment verified the effects of ethanol withdrawal on sleep-wakefulness. Significant increase in wakefulness was observed during ethanol withdrawal. Next, we examined c-Fos expression (marker of neuronal activation) in BF wake-promoting neurons during ethanol withdrawal. There was a significant increase in the number of BF wake-promoting neurons with c-Fos immunoreactivity. Our third experiment examined the effects of ethanol withdrawal on sleep deprivation induced increase in BF adenosine levels. Sleep deprivation did not increase BF adenosine levels in ethanol dependent rats. Our last experiment examined the effects of ethanol withdrawal on equilibrative nucleoside transporter 1 (ENT1) and A1 receptor (A1R) expression in the BF. There was a significant reduction in the A1R and ENT1 expression in the BF of ethanol dependent rats. Based on these results, we suggest that insomnia observed during ethanol withdrawal is caused due to impaired adenosinergic mechanism in the BF.
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期刊: NEUROSCIENCE
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