DNA Epigenetics in Addiction Susceptibility

Abstract

Addiction is a chronically relapsing neuropsychiatric disease that occurs in some, but not all, individuals who use substances of abuse. Relatively little is known about the mechanisms which contribute to individual differences in susceptibility to addiction. Neural gene expression regulation underlies the pathogenesis of addiction, which is mediated by epigenetic mechanisms, such as DNA modifications. A growing body of work has demonstrated distinct DNA epigenetic signatures in brain reward regions that may be associated with addiction susceptibility. Furthermore, factors that influence addiction susceptibility are also known to have a DNA epigenetic basis. In the present review, we discuss the notion that addiction susceptibility has an underlying DNA epigenetic basis. We focus on major phenotypes of addiction susceptibility and review evidence of cell type-specific, time dependent, and sex biased effects of drug use. We highlight the role of DNA epigenetics in these diverse processes and propose its contribution to addiction susceptibility differences. Given the prevalence and lack of effective treatments for addiction, elucidating the DNA epigenetic mechanism of addiction vulnerability may represent an expeditious approach to relieving the addiction disease burden.

Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention

“…Epigenetic modifications are likely to have particularly long lasting consequences to the brain when they occur during fetal or early infancy stages. This is because the enzymes mediat ing epigenetic modifications play a fundamental role in embry onic and postnatal brain development, so that their modification with in utero or early postnatal exposure to drugs might contrib ute to a higher vulnerability to addiction later in life 113 .…”

“…In parallel, studies are evaluating the effects of adverse envi ronmental exposures, such as stress and neglect, on epigenetic modifications. These are relevant for understanding the mecha nisms underlying the impact of such exposures on brain develop ment and their enhancement of the susceptibility to addiction 113 .…”

“…Though there are promising results from human positron emission tomography (PET) imaging studies that measured HDAC activity in the brain of healthy people, these measures have not yet been used to study SUDs 117‐119 . Clinical studies based on blood cells have found that individuals who consume drugs show epigenetic changes that appear to relate to the frequency of use in a dose‐dependent manner 113 . However, drug‐independent changes in addiction vulnerability triggered by adverse childhood experiences or other environmental factors might have also contributed to the epigenetic modifications reported in individuals with SUDs 120 .…”

Whole Genome DNA Methylation Profiling of D2 Medium Spiny Neurons in Mouse Nucleus Accumbens Using Two Independent Library Preparation Methods

“…With the advent of methylome profiling techniques, the spatiotemporal dynamics of DNA methylation during embryogenesis and development have been revealed to usually exist in cell type-specific patterns [ 22 , 23 , 24 , 25 , 26 ]. Accumulating evidence also implicates the role of DNA methylation in brain functions as well as in brain disorders, such as drug addiction [ 27 , 28 , 29 , 30 , 31 ]. Nucleus accumbens (NAc) is a key structure of the ventral striatum that plays a critical role in adaptive, goal-directed behaviors and mediates the seeking and using of addictive drugs [ 32 , 33 ].…”