Cognitive impairments by alcohol and sleep deprivation indicate trait characteristics and a potential role for adenosine A ₁ receptors

Abstract

Trait-like differences in cognitive performance after sleep loss put some individuals more at risk than others, the basis of such disparities remaining largely unknown. Similarly, interindividual differences in impairment in response to alcohol intake have been observed. We tested whether performance impairments due to either acute or chronic sleep loss can be predicted by an individual's vulnerability to acute alcohol intake. Also, we used positron emission tomography (PET) to test whether acute alcohol infusion results in an up-regulation of cerebral A adenosine receptors (AARs), similar to the changes previously observed following sleep deprivation. Sustained attention in the psychomotor vigilance task (PVT) was tested in 49 healthy volunteers (26 ± 5 SD years; 15 females) () under baseline conditions: () after ethanol intake, and after either () total sleep deprivation (TSD; 35 hours awake; = 35) or () partial sleep deprivation (PSD; four nights with 5 hours scheduled sleep; = 14). Ethanol- versus placebo-induced changes in cerebral AAR availability were measured in 10 healthy male volunteers (31 ± 9 years) with [F]8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine (CPFPX) PET. Highly significant correlations between the performance impairments induced by ethanol and sleep deprivation were found for various PVT parameters, including mean speed (TSD, = 0.62; PSD, = 0.84). AAR availability increased up to 26% in several brain regions with ethanol infusion. Our studies revealed individual trait characteristics for being either vulnerable or resilient to both alcohol and to sleep deprivation. Both interventions induce gradual increases in cerebral AAR availability, pointing to a potential common molecular response mechanism.

The role of adenosine receptors in mood and anxiety disorders

“…The increased signaling via A 1 receptors induced by SD leads to an enhanced formation of Homer1a in the mPFC, which mediates the antidepressant effects of SD (Serchov et al, ). However, SD in addition to its antidepressant effects also induces impairments in cognitive functions similar to those of ethanol which also induces an up‐regulation of cerebral A 1 adenosine receptors (Elmenhorst et al, ). In addition, SD in humans appears to increase state anxiety (Pires et al, ), but may induce rather a decrease in anxiety‐like behavior in preclinical models (Pires et al, ).…”

“…Disturbed sleep also negatively affects the immune system (Irwin and Opp, ) and induces elevation in brain inflammatory molecules such as interleukin 1‐β (IL‐1β) and tumor necrosis factor‐α (TNF‐α) and inhibition of BDNF (Zielinski et al, ). These negative effects of chronic SD on cognitive performance (Elmenhorst et al, ) appear to be mediated via effects on both adenosine A 1 and A 2A receptors (Urry and Landolt, ) and are at least in part modified by heritable individual differences (Krause et al, ). Indeed, there is evidence that prolonged A 1 receptor signaling and its cross‐talk with A 2A receptors may form the cellular basis for increased neurotoxicity in neurodegenerative disorders (Chen et al, ; Chen et al, ; Stockwell et al, ).…”

Effects of circadian misalignment on cognition in chronic shift workers

“…Chronic partial restriction of sleep (i.e., 2–3 h sleep loss per night accumulated over multiple nights) can also result in deficits of performance (i.e., sustained attention), particularly when there is limited opportunity for sleep recovery 12,16–20 . Further reductions in sleep duration impair performance even more, e.g., on sustained attention 18 , and may be similar in magnitude to alcohol intake 21,22 . The relevance of these sleep-induced effects on cognitive function is that night shift workers may be chronically sleep restricted, partly because of circadian misalignment 5 .…”

Research progress on adenosine in central nervous system diseases

“…The concentration of adenosine is reduced significantly after chronic stress, thus breaking the balance of its binding to A1R and A2AR. At low concentrations, adenosine mainly activates A1R, thereby inhibiting the release of 5‐HT, leading to a decrease in 5‐HT concentration in the hypothalamus and the occurrence of depression . Therefore, adenosine may not be directly involved in the antidepressant effect of sleep deprivation but affects its pathogenesis by regulating 5‐HT release.…”