The HPA axis and ethanol: a synthesis of mathematical modelling and experimental observations
Authorized Users Only
Markovic, Vladimir M.
Article (Published version)
MetadataShow full item record
Stress 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) oscillati...ons, 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.
Keywords:Alcohol or ethanol / blunted HPA axis response / corticotropin-releasing factor or corticotropin-releasing hormone / dynamical systems theory / HPA axis / opioid surfeit / stress
Source:Addiction Biology, 2017, 22, 6, 1486-1500
- Wiley, Hoboken
- Karolinska Institute Research Funds
- Swedish Research Council
- Knut and Alice Wallenberg Foundation
- Rajko and Maj Dermanovic Fund
- CMST COST Action CM 1304 'Emergence and Evolution of Complex Chemical Systems'
- Dynamics of nonlinear physicochemical and biochemical systems with modeling and predicting of their behavior under nonequilibrium conditions (RS-172015)
- Nanostructured Functional and Composite Materials in Catalytic and Sorption Processes (RS-45001)