Sex dependent alteration of epigenetic marks after chronic morphine treatment in mice organs.

Epigenetic marks may be also affected by several factors, such as age, lifestyle, early life experiences and exposure to chemicals or drugs, such as opioids. Previous studies have focused on how morphine epigenetically regulates different regions of the brain that are implicated in tolerance, dependence and other psychiatric disorders more related to the physio-pathological effects of opioids. Nevertheless, a significant knowledge gap remains regarding the effect of chronic treatment on other organs and biological systems. Therefore, the aim of this work is to increase our knowledge about the impact of chronic morphine exposure on DNA methylation and histone modification levels in each of the organs of male and female model mice in vivo. Our results reveal, for the first time, that chronic morphine treatment induced changes in DNA methylation/hydroxymethylation and histone modification in-vivo at the systemic level, revealing a potential physiological effect on the regulation of gene expression. Notably, morphine-induced epigenetic modification occurs in a sex-dependent manner, revealing the existence of different underlying mechanisms of epigenetic modification in male and female mice.