The Developmental Neuroepigenetics of Substance Abuse

Abstract

Advances in technology have allowed for the expansion of the field of epigenetics, providing a deeper understanding of geneenvironment interactions. Investigations into the neurobiological basis of substance abuse have benefitted from these advances, with findings suggesting that epigenetic mechanisms underlie drug-induced modifications of brain morphology, synaptic plasticity, and behavior. Epigenetic marks likely mediate the long-lasting and potentially transgenerational alterations of neuronal chromatin and subsequent gene expression that may lead to persistent relapse vulnerability and/or offspring vulnerability to addiction. Understanding the epigenetic mechanisms as well as potential sensitive windows for these alterations may provide novel insight into how epigenetics factor into the individual vulnerability and unique time periods for added vulnerability to illicit drug exposure. In the current review, we outline recent literature that provides evidence for early epigenetic changes in several addiction models. We begin the review with an overview of epigenetics as they relate to drug use and abuse, and next focus on findings in the context of prenatal, childhood, and adolescent stages with additional references to adult models of addiction. Further, we also focus on studies that discuss the transgenerational inheritance of epigenetic changes, and how they may affect the individual across development. Lastly, the work presented here and potential future studies focus on demonstrating early disruptions in epigenetic marks following acute or repeated drug exposure that may be of relevance in the broader goal of identifying risk factors and novel targets for addiction treatment.

Environmental Exposure during Pregnancy: Influence on Prenatal Development and Early Life: A Comprehensive Review

“…Prenatal drug use has been associated with microcephaly and adverse consequences for the foetus and (later) adolescent brains [43]; changes in brain morphology and synaptic plasticity have been reported [44], leading to lack of attention, reduced executive functioning skills, and disabilities in learning and memory, and consequently poorer academic attainment and behavioural problems [45-47]. Cannabis, cocaine, heroin, and methamphetamine are the most consumed substances.…”

Histone deacetylase inhibition differentially attenuates cue-induced reinstatement: An interaction of environment and acH3K9 expression in the dorsal striatum.

“…The field of epigenetics, at the nexus of gene-environment interactions, examines how environmental stimuli influence transcription and gene expression. Drugs of abuse alter gene expression, and epigenetic mechanisms have been investigated in preclinical models of drug abuse due to their ability to modulate the tendency to seek drug reward (Mason et al, 2018; Renthal et al, 2007; Robison & Nestler, 2011).…”