Alcohol disrupts sleep homeostasis

Abstract

Alcohol is a potent somnogen and one of the most commonly used “over the counter” sleep aids. In healthy non-alcoholics, acute alcohol decreases sleep latency, consolidates and increases the quality (delta power) and quantity of NREM sleep during the first half of the night. However, sleep is disrupted during the second half. Alcoholics, both during drinking periods and during abstinences, suffer from a multitude of sleep disruptions manifested by profound insomnia, excessive daytime sleepiness, and altered sleep architecture. Furthermore, subjective and objective indicators of sleep disturbances are predictors of relapse. Finally, within the USA, it is estimated that societal costs of alcohol-related sleep disorders exceeds $18 billion. Thus, although alcohol-associated sleep problems have significant economic and clinical consequences, very little is known about how and where alcohol acts to affect sleep. In this review, we have described our attempts to understand how and where alcohol acts to affect sleep. We have conducted a series of experiments using two different species, rats and mice, as animal models, and a combination of multi-disciplinary experimental methodologies to examine and understand anatomical and cellular substrates mediating the effects of acute and chronic alcohol exposure on sleep-wakefulness. The results of our studies suggest that the sleep-promoting effects of alcohol may be mediated via alcohol’s action on the mediators of sleep homeostasis: adenosine (AD) and the wake-promoting cholinergic neurons of the basal forebrain (BF). Alcohol, via its action on AD uptake, increases extracellular AD resulting in the inhibition of BF wake-promoting neurons. Lesions of the BF cholinergic neurons or blockade of AD A1 receptors results in attenuation of alcohol-induced sleep promotion, suggesting that AD and BF cholinergic neurons are critical for sleep-promoting effects of alcohol. Since binge alcohol consumption is a highly prevalent pattern of alcohol consumption and disrupts sleep, we examined the effects of binge drinking on sleep-wakefulness. Our results suggest that disrupted sleep homeostasis may be the primary cause of sleep disruption observed following binge drinking. Finally, we have also shown that insomnia and associated sleep disruptions, observed during acute withdrawal, are caused due to impaired sleep homeostasis. Based on our findings, we suggest that alcohol may disrupt sleep homeostasis to cause sleep disruptions.

Brain pathways to recovery from alcohol dependence

“…Although several sleep factors have been identified and implicated to mediate the build-up of sleep pressure during wakefulness, only adenosine has gained the utmost attention because adenosine links sleep with energy metabolism and neuronal activity (Thakkar et al, 2014). During wakefulness, energy (ATP) usage is high in wake-promoting systems, due to increased neuronal firing, synaptic activity, and synaptic potentiation.…”

“…This increased energy usage during wakefulness is reflected in increased accumulation of extracellular adenosine, a breakdown product of ATP metabolism, which corresponds to increased accumulation of sleep pressure. The longer the period of wakefulness, greater the accumulation of sleep pressure and/or AD and the longer it takes for sleep pressure to dissipate during sleep (Thakkar et al, 2014). …”

The association between insomnia and prescription opioid use: results from a community sample in Northeast Florida

“…Alcohol 19,34 , cigarette smoking 17 , depression 4 , anxiety 5 , older age 35 , and pain 6 have all been previously associated with insomnia. Specifically, multiple studies have linked pain to sleep disturbance and there is evidence of temporal precedence of sleep disturbances over pain.…”

“…Previous studies have investigated the relationship between some substances and disrupted sleep, including the association between sleep and cigarette smoking 17 , antihypertensive drugs 18 , alcohol 19 , benzodiazepines 20 , hypnotics and anxiolytics. 21 Common side effects from prescription opioid use are sleep disturbances such as SDB 22 and reduction in sleep efficiency.…”

Sleep Disturbances in Alcoholic Disease. Diagnpstics and Therapy

“…С одной стороны, адено-зин обеспечивает гомеостатические механизмы сна, с другой -является ключевым медиатором нейронального ответа на этанол. Изменение уровня аденозина имеет важное значение в симптомообразовании синдрома отмены алкоголя, в частности тревоги, тремора, судорож-ных приступов отмены [31]. Повышение уровня аденози-на вызывает сонливость, наступление фазы медленно-волновой активности и подавление REM-сна, а также алкоголь-индуцированной атаксии [24].…”