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dc.creatorČupić, Željko
dc.creatorStanojevic, Ana
dc.creatorMarkovic, Vladimir M.
dc.creatorKolar-Anić, Ljiljana
dc.creatorTerenius, Lars
dc.creatorVukojevic, Vladana
dc.date.accessioned2019-01-30T17:53:13Z
dc.date.available2019-01-30T17:53:13Z
dc.date.issued2017
dc.identifier.issn1355-6215
dc.identifier.urihttp://cer.ihtm.bg.ac.rs/handle/123456789/2087
dc.description.abstractStress and alcohol use are interrelatedstress contributes to the initiation and upholding of alcohol use and alcohol use alters the way we perceive and respond to stress. Intricate mechanisms through which ethanol alters the organism's response to stress remain elusive. We have developed a stoichiometric network model to succinctly describe neurochemical transformations underlying the stress response axis and use numerical simulations to model ethanol effects on complex daily changes of blood levels of cholesterol, 6 peptide and 8 steroid hormones. Modelling suggests that ethanol alters the dynamical regulation of hypothalamic-pituitary-adrenal (HPA) axis activity by affecting the amplitude of ultradian oscillations of HPA axis hormones, which defines the threshold with respect to which the response to stress is being set. These effects are complexlow/moderate acute ethanol challenge ( LT 8mM) may reduce, leave unaltered or increase the amplitude of ultradian cortisol (CORT) oscillations, giving rise to an intricate response at the organism level, offering also a potential explanation as to why apparently discordant results were observed in experimental studies. In contrast, high-dose acute ethanol challenge (> 8mM) increases instantaneous CORT levels and the amplitude of ultradian CORT oscillations in a dose-dependent manner, affecting the HPA axis activity also during the following day(s). Chronic exposure to ethanol qualitatively changes the HPA axis dynamics, whereas ethanol at intoxicating levels shuts down this dynamic regulation mechanism. Mathematical modelling gives a quantitative biology-based framework that can be used for predicting how the integral HPA axis response is perturbed by alcohol.en
dc.publisherWiley, Hoboken
dc.relationKarolinska Institute Research Funds
dc.relationSwedish Research Council
dc.relationKnut and Alice Wallenberg Foundation
dc.relationRajko and Maj Dermanovic Fund
dc.relationCMST COST Action CM 1304 'Emergence and Evolution of Complex Chemical Systems'
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172015/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/45001/RS//
dc.rightsrestrictedAccess
dc.sourceAddiction Biology
dc.subjectAlcohol or ethanolen
dc.subjectblunted HPA axis responseen
dc.subjectcorticotropin-releasing factor or corticotropin-releasing hormoneen
dc.subjectdynamical systems theoryen
dc.subjectHPA axisen
dc.subjectopioid surfeiten
dc.subjectstressen
dc.titleThe HPA axis and ethanol: a synthesis of mathematical modelling and experimental observationsen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractВукојевиц, Владана; Колар-Aниц, Љиљана; Станојевиц, Aна; Марковиц, Владимир М.; Чупић, Жељко; Терениус, Ларс;
dc.citation.volume22
dc.citation.issue6
dc.citation.spage1486
dc.citation.epage1500
dc.citation.other22(6): 1486-1500
dc.citation.rankaM21
dc.identifier.pmid27189379
dc.identifier.doi10.1111/adb.12409
dc.identifier.rcubConv_3821
dc.identifier.scopus2-s2.0-84969922983
dc.identifier.wos000413904600002
dc.type.versionpublishedVersion


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