Amphetamine exposure during development causes epigenetic trans‐generational changes in drug sensitivity in Caenorhabditis elegans (803.8)

Abstract

It’s well known that psychostimulants like amphetamine (AMPH) increase the amount of dopamine in the synaptic cleft. In C. elegans, it has been shown that a dopamine increase in the synapses causes a unique behavior named swimming induced paralysis (SWIP). Previous studies demonstrated that SWIP is a valid tool to investigate the effect of addictive drugs. Here, we explored the response to AMPH in C. elegans adult animals following previous exposure to the drug during development, as well as the second generation to see if a change in response was passed to progeny. Our results show that adult animals (F0) exposed to AMPH during development had a higher AMPH‐induced SWIP with respect to control‐exposed animals. Further, we found an elevated SWIP response in the second generation (F1) of animals originated from maternal lines that were exposed to AMPH during development. Epigenetic mechanisms were investigated to explain the inherited change in response to AMPH. Histone3 Lys4 trimethylation (H3K4me3) and histone3 Lys27 (H3K27me3) are promoter‐specific histone modifications associated with active transcription and gene repression, respectively. To test if H3K4 or H3K27 methylation were a contributing factor in the increased SWIP response seen after AMPH exposure, we performed western blot assays against H3K4me3 and H3K27me3 in protein samples collected from F0 and F1 animals. Our data shows that AMPH exposure during development decreases H3K4me3 expression in the F1 generation, while no change is seen in H3K27. These results suggest that epigenetic mechanisms underlie the trans‐generational effects induced by AMPH. Other epigenetic markers are currently under investigation.Grant Funding Source: Supported by P20 GM104360‐1 NIH Grant