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Impact of Genetic Variation on Stress‐Related Ethanol Consumption
Author(s) -
Mulligan Megan K.,
Lu Lu,
Cavigelli Sonia A.,
Mormède Pierre,
Terenina Elena,
Zhao Wenyuan,
Williams Robert W.,
Jones Byron C.
Publication year - 2019
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.14073
Subject(s) - stressor , population , quantitative trait locus , alcohol , ethanol , genetics , biology , physiology , chronic stress , endocrinology , medicine , gene , biochemistry , environmental health , neuroscience
Background The effect of stress on alcohol consumption in humans is highly variable, and the underlying processes are not yet understood. Attempts to model a positive relationship between stress and increased ethanol (EtOH) consumption in animals have been only modestly successful. Our hypothesis is that individual differences in stress effects on EtOH consumption are mediated by genetics. Methods We measured alcohol consumption, using the drinking‐in‐the‐dark ( DID ) paradigm in females from 2 inbred mouse strains, C57 BL /6J ( B 6) and DBA /2J ( D 2), and 35 of their inbred progeny (the BXD family). A control group was maintained in normal housing and a stress group was exposed to chronic mild stress ( CMS ), consisting of unpredictable stressors over 7 weeks. These included predator, social, and environmental perturbations. Alcohol intake was measured over 16 weeks in both groups during baseline (preceding 5‐week period), CMS (intervening 7‐week period), and post‐CMS (final 4‐week period). Results We detected a strong effect of CMS on alcohol intake. A few strains demonstrated CMS ‐related increased alcohol consumption; however, most showed decreased intake. We identified 1 nearly significant quantitative trait locus on chromosome 5 that contains the neuronal nitric oxide synthase gene ( Nos1 ). The expression of Nos1 is frequently changed following alcohol exposure, and variants in this gene segregating among the BXD population may modulate alcohol intake in response to stress. Conclusions The results we present here represent the first study to combine chronic stress and alcohol consumption in a genetic reference population of mice. Differences in susceptibility to the effects of stressful environments vis‐à‐vis alcohol use disorders would suggest that the differences have at least some basis in genetic constitution. We have also nominated a likely candidate gene underlying the large individual differences in effects of stress on alcohol consumption.