Epigenetic regulation in drug addiction
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Chief Sanitary Inspectorate, Warsaw, Poland
Institute of Haematology and Transfusion Medicine, Warsaw, Poland
Department of Health Promotion, Food and Nutrition, Institute of Rural Health, Lublin, Poland
Independent Laboratory of Molecular Biology, Institute of Rural Health, Lublin, Poland
Department of Public Health, University of Information Technology and Management, Rzeszow, Poland
Specialist Outpatient Department for Rural Occupational Diseases, Institute of Rural Health, Lublin, Poland
Studium Generale Sandomiriense, Sandomierz, Poland
Corresponding author
Lucyna Kapka-Skrzypczak   

Independent Laboratory of Molecular Biology, Institute of Rural Health, Lublin, Poland
Ann Agric Environ Med. 2012;19(3):491-496
The interaction between environmental signals and genes has now taken on a clear molecular form as demonstrated by stable changes in chromatin structure. These changes occur through activation or repression of specific gene programmes by a combination of chromatin remodelling, activation and enzymatic modification of DNA and histones as well as nucleosomal subunit exchange. Recent research investigating the molecular mechanisms controlling drug-induced transcriptional, behavioural and synaptic activity has shown a direct role for chromatin remodelling – termed as epigenetic regulation – of neuronal gene programmes and subsequent addictive behaviour arising from it. Recent data suggest that repeated exposure to certain drugs promotes changes in levels of histone acetylation, phosphorylation and methylation, together with alterations in DNA methylation levels in the neurons of the brain reward centre, localised in the Nucleus Accumbens (NAc) region of the limbic system. The combination of acetylating, phosphorylating and methylating H3 and H4 histone tails alter chromatin compaction thereby promoting altered levels of cellular gene expression. Histone modifications, which weaken histone interaction with DNA or that promote recruitment of transcriptional activating complexes, correlate with permissive gene expression. Histone deacetylation, (which strengthen histone: DNA contacts), or histone methylation, (which recruits repressive complexes to chromatin), promote a state of transcriptional repression. Using animal models, acute cocaine treatment increases H4 acetylation at acutely regulated gene promoters, whereas H3 acetylation appears to predominate at chronically induced promoters. Chronic cocaine and alcohol treatment activate and repress many genes such as FosB, Cdk5, and Bdnf, where their dysregulation, at the chromatin level, contribute to the development and maintenance of addiction. Following drug exposure, it is still unknown, howver, how long these changes in chromatin structure persist in affecting neuronal function, but some do so for life.
Waddington CH. (Ed.) The discussion of some aspects of theoretical biology of the genes. Allen & Unwin. London. 1957.
Bygren LO, Kaati G, Edvinsson S. Longevity determined by paternal ancestors’ nutrition during their slow growth period. Acta Biotheor. 2001; 49(1): 53-9.
Kaati G, Bygren LO, Edvinsson S.Cardiovascular and diabetes mortality determined by nutrition during parents’ and grandparents’ slow growth period. Eur J Hum Genet. 2002; 10(11): 682-8.
Pembrey ME, Bygren LO, Kaati G, Edvinsson S, Northstone K, Sjöström M, et al. Sex-specific, male-line transgenerational responses in humans. Eur J Hum Genet. 2006; 14(2): 159-66.
Kwinecka-Dmitriew B, Zakrzewska M, Latos-Bieleńska A, Skrzypczak J. Frequency of chromosomal aberrations in material from abortions. Ginekol Pol. 2010; 81(12): 896-901.
Iciek R, Wender-Ożegowska E, Zawiejska A, Seremak-Mrozikiewicz A, Drews K, Brązert J. The influence of metabolic parameters on fetal development weight in women with type 1 diabetes and homozygotic variant in -2548 G/A of leptin gene and its 668 A/G receptor polymorphism. Ginekol Pol. 2010; 81(08): 571-577.
Goldberg AD, Allis CD, Bernstein E. Epigenetics: a landscape takes shape. Cell. 2007; 128(4): 635-8.
Dambacher S, Hahn M, Schotta G. Epigenetic regulation of development by histone lysine methylation.Heredity (Edinb). 2010; 105(1): 24-37.
Cheung P, Allis CD, Sassone-Corsi P. Signaling to chromatin through histone modifications. Cell. 2000; 103(2): 263-71.
Robison AJ, Nestler EJ. Transcriptional and epigenetic mechanisms of addiction. Nat Rev Neurosci. 2011; 12(11): 623-37.
Kouzarides T. Chromatin modifications and their function. Cell. 2007; 128(4): 693-705.
Powledge T. Behavioral epigenetics: How nurture shapes nature. BioScience. 2011; 61(8): 588-592.
Jenuwein T, Allis CD. Translating the histone code. Science. 2001; 293(5532): 1074-80.
Miller G. Epigenetics. The seductive allure of behavioral epigenetics. Science 2010; 329(5987): 24-7.
Renthal W, Nestler EJ. Epigenetic mechanisms in drug addiction. Trends Mol Med. 2008; 14(8): 341-50.
Samochowiec A, Mordasiewicz A, Arentowicz G, Samochowiec J. Wpływ badań genetycznych na poznanie patogenezy uzależnień. Psychiatria 2005; 2: 9-18.
Samochowiec J. Czynniki genetyczne w uzależnieniu alkoholowym. Neuropsychiatria i Neuropsychologia 2007; 2: 54-56.
Vetulani J. Drug addiction. Part II. Neurobiology of addiction. Pol J Pharmacol. 2001; 53(4): 303-17.
Przewoźniak K, Łobaszewski J, Wojtyła A, Bylina J, Mańczuk M, Zatoński WA. Alcohol drinking patterns and habits among a sample of PONS study subjects: preliminary assessment Ann Agric Environ Med. 2011; 18(2): 221-228.
Mehler MF. Epigenetic principles and mechanisms underlying nervous system functions in health and disease”. Prog. Neurobiol. 2008; 86(4): 305-41.
Kapka-Skrzypczak L, Kulpa P, Sawicki K, Cyranka M, Wojtyła A, Kruszewski M. Legal highs – legal aspects and legislative solutions. Ann Agric Environ Med. 2011; 18(2): 304-309.
Chang TY, Meaney MJ. Epigenetics and the environmental regulation of the genome and its function. Annu Rev Psychol. 2010; 61: 439-66, C1–3.
Sun J, Sun J, Ming GL, Song H. Epigenetic regulation of neurogenesis in the adult mammalian brain. Eur. J. Neurosci. 2011; 33(6): 1087-93.
Kumar A, Choi KH, Renthal W, Tsankova NM, Theobald DE, Truong HT et al. Chromatin remodeling is a key mechanism underlying cocaine-induced plasticity in striatum. Neuron. 2005; 48(2): 303-14.
Nestler EJ. Transcriptional mechanisms of addiction: role of ΔFosB. Philos Trans R Soc Lond B Biol Sci. 2008; 363(1507): 3245-3255.
Cheung P, Allis CD, Sassone-Corsi P. Signaling to chromatin through histone modifications. Cell. 2000; 103(2): 263-7.
Nestler EJ, Barrot M, Self DW. DeltaFosB: a sustained molecular switch for addiction. Proc Natl Acad Sci U S A. 2001; 98(20): 11042-6.
Maze I, Nestler EJ. The epigenetic landscape of addiction. Ann N Y Acad Sci. 2011; 1216: 99-113.
Perrotti LI, Weaver RR, Robison B, Renthal W, Maze I, Yazdani S et al. Distinct Patterns of ΔFosB Induction in Brain by Drugs of Abuse. Synapse. 2008; 62(5): 358-369.
O›Callaghan FV, Al Mamun A, O›Callaghan M, Alati R, Najman JM, Williams GM, Bor W. Maternal smoking during pregnancy predictsnicotine disorder (dependence or withdrawal) in young adults – a birth cohort study. Aust N Z J Public Health. 2009; 33(4): 371-7.
Agrawal A, Scherrer JF, Grant JD, Sartor CE, Pergadia ML, Duncan AE, Madden PA, Haber JR, Jacob T, Bucholz KK, Xian H. The effects of maternal smoking during pregnancy on offspring outcomes. Prev Med. 2010; 50(1-2): 13-8.
Ernst M, Moolchan E, Robinson M. Behavioral and neural consequences of parental exposure to nicotine. J Am Acad Child Adolesc Psychiatry. 2001; 40: 630-641.
Cornelius MD, Leech SL, Goldschmidt L, Day NL. Prenatal tobacco exposure: is it a risk factor for early tobacco experimentation? Nicotine Tob Res. 2000; 2(1): 45-52.
Ebrahim SH, Floyd RL, Merritt RK 2nd, Decoufle P, Holtzman D. Trends in pregnancy-related smoking rates in the United States, 1987-1996. JAMA. 2000; 283(3): 361-6.
Sochaczewska D, Czeszyńska M, Konefał H, Garanty-Bogacka B. Maternal active or passive smoking in relation to some neonatal morphological parameters and complications. Ginekol Pol. 2010; 81(09): 687-692.
Lieb R, Merikangas KR, Höfler M, Pfister H, Isensee B, Wittchen HU. Parental alcohol use disorders and alcohol use and disorders in offspring: a community study. Psychol Med. 2002; 32(1): 63-78.
Fischer D, Solbach C, Kitz R, Ahr A, Veldman A. Acute ethanol intoxication during pregnancy and consecutive fetal cardiac arrest: a case report. J Perinat Med. 2003; 31(4): 343-4.
Czech E, Hartleb M. Poalkoholowe Uszkodzenia Płodu Jako Niedoceniana Przyczyna Wad Rozwojowych i Zaburzeń Neurobehawioralnych u Dzieci. Alkohol Narkom. 2004; 17(1-2): 9-20.
Merikangas KR, Dierker LC, Szatmari P. Psychopathology among offspring of parents with substance abuse and/or anxiety disorders: a high-risk study. J Child Psychol Psychiatry. 1998; 39(5): 711-20.
Lester BM, Lagasse LL. Children of addicted women. J Addict Dis. 2010; 29(2): 259-76.
Barker DJ. The developmental origins of adult disease. J Am Coll Nutr. 2004; 23(6 Suppl): 588S-595S.
Wojtyła A. Application of the hypothesis of Developmental Origin of Health and Diseases (DOHaD) in epidemiological studies of women at reproductive age and pregnant women in Poland. Ann Agric Environ Med. 2011; 18(2): 355-364.
Wojtyła A, Kapka-Skrzypczak L, Paprzycki P, Skrzypczak M, Biliński P. Epidemiological studies in Poland on effect of physical activity of pregnant women on the health of offspring and future generations – adaptation of the hypothesis Development Origin of Health and Diseases. Ann Agric Environ Med. 2012; 19(2): 315-326.
Berlander TF, Weinberg J, Papsdorf M, Grunau R, Misri S, Devlin AM. Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses“. Epigenetics. 2008; 3(2): 97-106.
Barker DJ. Developmental origins of adult health and disease. J Epidemiol Community Health. 2004; 58(2): 114-5.
Najman JM, Bor W, O‘Callaghan M, Williams GM, Aird R, Shuttlewood G. Cohort Profile: The Mater-University of Queensland Study of Pregnancy (MUSP). Int J Epidemiol. 2005; 34(5): 992-7.
Wojtyła A, Kapka-Skrzypczak L, Biliński P, Paprzycki P. Physical activity among women at reproductive age and during pregnancy (Youth Behavioural Polish Survey – YBPS and Pregnancy-related Assessment Monitoring Survay – PrAMS) – epidemiological population studies in Poland during the period 2010-2011. Ann Agric Environ Med. 2011; 18(2): 365-374.
Lester BM, Padbury JF. Third pathophysiology of prenatal cocaine exposure. Dev Neurosci. 2009; 31(1-2): 23-35.
Barker DJ, Osmond C, Rodin I, Fall CH, Winter PD. Low weight gain in infancy and suicide in adult life. BMJ. 1995; 311(7014): 1203.
Gluckman PD, Hanson MA. Living with the past: evolution, development, and patterns of disease. Science. 2004; 305(5691): 1733-6.
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