Epigenetics: a link between addiction and social environment - PubMed (original) (raw)

Review

Duyilemi C Ajonijebu et al. Cell Mol Life Sci. 2017 Aug.

Abstract

The detrimental effects of drug abuse are apparently not limited to individuals but may also impact the vulnerability of their progenies to develop addictive behaviours. Epigenetic signatures, early life experience and environmental factors, converge to influence gene expression patterns in addiction phenotypes and consequently may serve as mediators of behavioural trait transmission between generations. The majority of studies investigating the role of epigenetics in addiction do not consider the influence of social interactions. This shortcoming in current experimental approaches necessitates developing social models that reflect the addictive behaviour in a free-living social environment. Furthermore, this review also reports on the advancement of interventions for drug addiction and takes into account the emerging roles of histone deacetylase (HDAC) inhibitors in the etiology of drug addiction and that HDAC may be a potential therapeutic target at nucleosomal level to improve treatment outcomes.

Keywords: Chromatin remodeling; Cocaine and alcohol abuse; DNA methylation; Environmental stimuli; Epigenomic programming and inheritance; Social stress.

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Conflict of interest statement

All authors have no conflict of interest to disclose.

Figures

Fig. 1

Fig. 1

Schematic view of post-translational modifications of histones. a In eukaryotic cells, the DNA (consists of 147 base pairs) wraps around histone octamers (two copies each of H2A, H2B, H3, and H4) to form the nucleosome which is the functional unit of the chromatin. Projecting from the core of the histone octamers is the amino acid (-N-) terminal tails on which significant transcriptional modification occurs. b Transcriptional active or inactive states of the chromatin are balanced by the opposing actions of HATs and HDACs, respectively. Enhanced action of HATs promotes histone acetylation which allows assessibility of the DNA to the transcription factors by relaxing the chromatin resulting in an enhanced gene activity. Conversely, increased action of HDACs represses transcription (gene silencing) by deacetylating the histones. HDAC5 is one the II HDACs that shuttles between the nucleus and the cytoplasm and actively mediates gene silencing mechanism by binding hormone co-repressors. Consequently, nuclear export of HDAC5 which results in histone hyperacetylation as well as increased mRNA expression of its target genes (e.g., substance P and neurokinin 1) have been critically implicated in sensitized behavioural responses to addictive drugs [57]. In addition, toxicants such as drugs or endocrine disruptors can induce epimutations of the histone octamers [73] resulting in chromosomal abnormalities that are fundamental to addiction phenotypes and disease

Fig. 2

Fig. 2

Model of possible factors that influence drug intake. Altered states in the environment influenced by various factors, such as physical contact, gender, family history, social or early life experience all converge to impact on the individual’s sensitivity and vulnerability to addictive compounds. In contrast, escalated or chronic drug intake especially at high doses possibly induces changes that accumulate over time to promote further drug use or addictive behaviours and sometimes may be passed down the germline to the next generation. Invariably, behavioural (drug intake) and psychological (vulnerability) balance largely depends on the level of exposure to drugs and associated factorial states within the environment

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References

    1. Everitt BJ, Robbins TW. Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat Neurosci. 2005;8(11):1481–1489. doi: 10.1038/nn1579. - DOI - PubMed
    1. Lieb R (2015) Epidemiological perspectives on comorbidity between substance use disorders and other mental disorders. In: Dom G, Moggi F (eds) Co-occurring Addictive and Psychiatric Disorders. Springer, Heidelberg, pp 3–12
    1. Nelson PK, et al. Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews. Lancet. 2011;378(9791):571–583. doi: 10.1016/S0140-6736(11)61097-0. - DOI - PMC - PubMed
    1. Compton WM, et al. Developments in the epidemiology of drug use and drug use disorders. Am J Psychiatry. 2005;162(8):1494–1502. doi: 10.1176/appi.ajp.162.8.1494. - DOI - PubMed
    1. Renthal W, Nestler EJ. Epigenetic mechanisms in drug addiction. Trends Mol Med. 2008;14(8):341–350. doi: 10.1016/j.molmed.2008.06.004. - DOI - PMC - PubMed

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