title: Role of adenosine and wake-promoting basal forebrain in insomnia and associated sleep disruptions caused by ethanol dependence.
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.
authors.affiliation: Harry S. Truman Memorial Veterans Hospital and Department of Neurology, University of Missouri, Columbia, Missouri 65210, USA.
authors.forename: Rishi
authors.initials: R
authors.lastname: Sharma
authors.forename: Samuel
authors.initials: S
authors.lastname: Engemann
authors.forename: Pradeep
authors.initials: P
authors.lastname: Sahota
authors.forename: Mahesh M
authors.initials: MM
authors.lastname: Thakkar
mesh_terms: D000241:Adenosine / Q000378:metabolism / Q000502:physiology*; D000437:Alcoholism / Q000150:complications* / Q000503:physiopathology*; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis; D002452:Cell Count; D033721:Equilibrative Nucleoside Transporter 1; D007150:Immunohistochemistry; D008297:Male; D017551:Microdialysis; D016548:Prosencephalon / Q000503:physiopathology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012890:Sleep / Q000502:physiology; D012892:Sleep Deprivation; D007319:Sleep Initiation and Maintenance Disorders / Q000209:etiology* / Q000503:physiopathology*; D012893:Sleep Wake Disorders / Q000209:etiology* / Q000503:physiopathology*; D012895:Sleep, REM / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000523:psychology; D014851:Wakefulness / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D033721:Equilibrative Nucleoside Transporter 1; D016760:Proto-Oncogene Proteins c-fos; D043682:Receptor, Adenosine A1; C438652:Slc29a1 protein, rat; D012313:RNA; D000241:Adenosine
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