Transgenerational effects of alcohol on intoxication sensitivity in Caenorhabditis elegans

Abstract

Alcohol abuse and dependence have a substantial heritable component. Although the genome has been considered the sole vehicle of heritable phenotypes, recent studies suggest that drug or alcohol exposure may induce alterations in gene expression that are transmitted across generations. Still, the transgenerational impact of alcohol use (and abuse) remains largely unexplored in part because multigenerational studies using rodent models present challenges for time, sample size, and genetic heterogeneity. Here, we took advantage of the extremely short generation time, large broods, and clonal form of reproduction of the nematode Caenorhabditis elegans. We developed a model of preconception parental alcohol exposure to test alterations in behavioral responses to acute alcohol treatment (intoxication) in subsequent F1, F2 and F3 generations. We found that a chronic alcohol-treatment paradigm in the parental generation resulted in alcohol-naive F3 progeny displaying moderate resistance to intoxication. To compare the treatment duration and timing on this transgenerational effect, we repeated the study using an intermittent treatment paradigm. We found that intermittent treatment resulted in alcohol-naive F3 progeny displaying moderate hypersensitivity to intoxication. Further study of this phenomena using this new C. elegans model may yield mechanistic insights into how transgenerational effects may occur in other animals.