title: Epigenetic Mechanisms of Psychostimulant-Induced Addiction.
abstract: Psychostimulant-induced addiction involves potentially life-long behavioral abnormalities that are caused by repeated exposure to a drug of abuse in vulnerable individuals. The persistence of these behavioral changes suggests that long-lasting alterations in gene expression, particularly within the brain's reward regions, may contribute significantly to the addiction phenotype. An increasing number of works over the past decade have demonstrated the important role of epigenetic regulatory events in mediating the lasting effects of drugs of abuse (including psychostimulants, such as cocaine and amphetamine) in animal models of drug addiction. In this review, we have introduced the importance of epigenetic processes in regulating gene expression and have described the role that dynamic epigenetic changes may play in psychostimulant-induced addiction via long-lasting transcriptional changes following repeated drug exposure. We overviewed the evidence showing that repeated exposure to psychostimulants induces three major modes of epigenetic regulation within the brain's reward regions-histone modification, DNA methylation, and noncoding RNAs. In several instances, it has been possible to demonstrate directly the contribution of these epigenetic changes to psychostimulant-related behavioral abnormalities. Studies of epigenetics may also help to determine the role environmental factors play in an individual's vulnerability to addiction. Further studies are required to validate these epigenetic changes in human addiction and to evaluate the possibility of developing new diagnostic tests and more effective treatments for addiction syndromes.
authors.affiliation: Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia. Electronic address: anti.kalda@ut.ee.
authors.forename: Anti
authors.initials: A
authors.lastname: Kalda
authors.affiliation: Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Zharkovsky
mesh_terms: D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D019175:DNA Methylation / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006657:Histones / Q000378:metabolism; D006801:Humans; D022661:RNA, Untranslated / Q000235:genetics; D019966:Substance-Related Disorders / Q000235:genetics*
chemical_list: D000697:Central Nervous System Stimulants; D006657:Histones; D022661:RNA, Untranslated
keywords: Chromatin structure; DNA methylation; Epigenetics; Gene expression; Histone modifications; Noncoding RNA; Psychostimulant-induced addiction