Abstract
Stress-related psychiatric disorders such as major depression are strongly associated with alcohol abuse and alcohol use disorder. Recently, many epidemiological and preclinical studies suggest that chronic stress prior to conception has cross-generational effects on the behavior and physiological response to stress in subsequent generations. Thus, we hypothesized that chronic stress may also affect ethanol drinking behaviors in the next generation. In the first cohort of mice, we found that paternal preconception chronic variable stress significantly reduced both two-bottle choice and binge-like ethanol drinking selectively in male offspring. However, these results were not replicated in a second cohort that were tested under experimental conditions that were nearly identical, except for one notable difference. Cohort 1 offspring were derived from in-house C57BL/6J sires that were born in the animal vivarium at the University of Pittsburgh whereas cohort 2 offspring were derived from C57BL/6J sires shipped directly from the vendor. Therefore, a third cohort that included both in-house and vendor born sires was analyzed. Consistent with the first two cohorts, we observed a significant interaction between chronic stress and sire-source with only stressed sires that were born in-house able to impart reduced ethanol drinking behaviors to male offspring. Overall, these results demonstrate that paternal preconception stress can impact ethanol drinking behavior in males of the next generation. These studies provide additional support for a recently recognized role of the paternal preconception environment in shaping ethanol drinking behavior.
Highlights
Over the last several years, there has been a burgeoning interest in epigenetic inheritance; that is, the transfer of acquired traits from parent to child via nongenomic germline mechanisms
Strain 129 females were utilized to remain consistent with previous studies examining intergenerational effects of stress and ethanol exposures (Rodgers et al, 2013; Finegersh and Homanics, 2014; FIGURE 1 | Intergenerational effects of paternal preconception chronic stress. (A) Experimental timeline
We found that paternal preconception chronic variable stress exposure attenuated ethanol drinking behavior selectively in male offspring
Summary
Over the last several years, there has been a burgeoning interest in epigenetic inheritance; that is, the transfer of acquired traits from parent to child via nongenomic germline mechanisms. Several epidemiological findings suggest that preconception stress affects offspring development and stress sensitivity (Bowers and Yehuda, 2016). Paternal Stress Reduces Ethanol Drinking by wide-ranging preclinical studies illustrating that the paternal preconception environment imparts diverse behavioral phenotypes to offspring as recently reviewed in Chan et al (2018). As these studies are largely carried out with isogenic mice or rats, the intergenerational effects are unlikely to be explained by genetic variation. Paternal chronic corticosterone (CORT) exposure increases anxiety-related behaviors in offspring (Short et al, 2016) and many of these paternal stress exposures alter hypothalamic-pituitary-adrenal (HPA) axis function in offspring (Dietz et al, 2011; Pisu et al, 2013; Rodgers et al, 2013; Gapp et al, 2016)
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