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Role of adenosine and wake‐promoting basal forebrain in insomnia and associated sleep disruptions caused by ethanol dependence
Author(s) -
Sharma Rishi,
Engemann Samuel,
Sahota Pradeep,
Thakkar Mahesh M.
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.06980.x
Subject(s) - adenosinergic , wakefulness , sleep deprivation , basal forebrain , medicine , endocrinology , privation , adenosine , ethanol , insomnia , adenosine receptor , psychology , chemistry , receptor , pharmacology , neuroscience , circadian rhythm , central nervous system , biochemistry , electroencephalography , agonist
J. Neurochem. (2010) 115 , 782–794. Abstract Insomnia is a severe symptom of alcohol withdrawal; however, the underlying neuronal mechanism is yet unknown. We hypothesized that chronic ethanol exposure will impair basal forebrain (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 and A1 receptor expression in the BF. There was a significant reduction in A1 receptor and equilibrative nucleoside transporter 1 expression in the BF of ethanol dependent rats. Based on these results, we suggest that insomnia observed during ethanol withdrawal is caused because of impaired adenosinergic mechanism in the BF.