The Generational Hangover: The Epigenetic Consequences of Adolescent Opioid Abuse

Abstract

The number of Americans addicted to opioids is rising (NIDA 2023). The consequences on an individual’s health are well studied, but research into changes in gene expression, epigenetics, and opioid addiction is lacking. Regarding the F0 generation, the generation exposed to the opioids, there is existing research on the transgenerational effects of opioid addiction, including studies that have outlined the F0 sex-based effects of opioid abuse on the F1 generation of rats. However, the mechanism by which these effects are passed from one generation to the next is unknown. In this paper, I investigated the consequences of adolescent opioid abuse in the F0 generation. I examined the endogenous opioid genes in the reproductive systems of both male and female rats to determine if morphine abuse during adolescence causes dysregulations in these genes. In addition, I researched the gene MeCP2, which is responsible for gene regulation and chromatin remodeling. My results showed that in the testes of adolescent male rats, the mu and kappa opioid receptors, two of the main endogenous opioid receptors in the body, were dysregulated. I performed immunohistochemistry (IHC) staining to analyze the intensity of MeCP2 in the testes, which was also dysregulated. Additional work done by Dr. Fair Vassoler showed that miR-Let-7, a major regulatory miRNA in the endogenous opioid system, was dysregulated in both the testes and the sperm of the males. This paper makes three main contributions to the literature on the epigenetic consequences of opioid abuse. First, it provides preliminary evidence of changes in gene regulation in the male reproductive systems of rats that were exposed to morphine during adolescence (Mor-F0). Second, it shows that there are sex-based differences in gene expression after morphine exposure. Finally, it provides preliminary evidence of changes to the gene expression in the F1 generation. In doing so, this paper presents a possible mechanism of heritability for the sex-based behavioral effects seen in previous studies (Vassoler et al., 2016, Vassoler et al., 2020).