Abstract
Substance use disorders (SUDs) is characterized by the deregulation of motivational brain circuits and involves neuroadaptation processes that contribute to the transition from controlled to compulsive consumption of drugs of abuse. Such neuroadaptations are consolidated in long-term changes due to changes in gene expression regulation. These changes are regulated by the chromatin structure and epigenetic changes in the DNA and histone proteins that make up the chromatin. The epigenetic mechanisms control the space between the nucleosomes and the levels of their condensation allowing the access of the transcriptional machinery to the promoter of a specific gene. In recent decades, studies with animal models have shown that the use of drugs of abuse can trigger epigenetic changes in several brain regions important for the perpetuation of the addiction cycle. This chapter discusses neurobiological aspects and epigenetic mechanisms, such as DNA methylation and post-translational modifications of histones involved in SUDs.
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References
Abrahao, K. P., Salinas, A. G., & Lovinger, D. M. (2017). Alcohol and the brain: Neuronal molecular targets, synapses, and circuits. Neuron, 96(6), 1223–1238. https://doi.org/10.1016/j.neuron.2017.10.032.
Adinoff, B. (2004). Neurobiologic processes in drug reward and addiction. Harvard Review of Psychiatry, 12(6), 305–320. https://doi.org/10.1080/10673220490910844.
Aguilar-Valles, A., Vaissière, T., Griggs, E. M., Mikaelsson, M. A., Takács, I. F., Young, E. J., et al. (2014). Methamphetamine-associated memory is regulated by a writer and an eraser of permissive histone methylation. Biological Psychiatry, 76(1), 57–65. https://doi.org/10.1016/j.biopsych.2013.09.014.
Alam, H., Gu, B., & Lee, M. G. (2015). Histone methylation modifiers in cellular signaling pathways. Cellular and Molecular Life Sciences: CMLS, 72(23), 4577–4592. https://doi.org/10.1007/s00018-015-2023-y.
Allis, C. D., & Jenuwein, T. (2016). The molecular hallmarks of epigenetic control. Nature Reviews Genetics, 17(8), 487–500. https://doi.org/10.1038/nrg.2016.59.
American Psychiatric Association (APA). (2014). Manual diagnóstico e estatístico de transtornos mentais (5th ed.). Porto Alegre, Brazil: Artmed Editora.
Becker, J. B., & Chartoff, E. (2019). Sex differences in neural mechanisms mediating reward and addiction. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 44(1), 166–183. https://doi.org/10.1038/s41386-018-0125-6.
Bohnsack, J. P., Hughes, B. A., O’Buckley, T. K., Edokpolor, K., Besheer, J., & Morrow, A. L. (2018). Histone deacetylases mediate GABAA receptor expression, physiology, and behavioral maladaptations in rat models of alcohol dependence. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 43(7), 1518–1529. https://doi.org/10.1038/s41386-018-0034-8.
Bourguet, E., Ozdarska, K., Moroy, G., Jeanblanc, J., & Naassila, M. (2018). Class I HDAC inhibitors: Potential new epigenetic therapeutics for alcohol use disorder (AUD). Journal of Medicinal Chemistry, 61(5), 1745–1766. https://doi.org/10.1021/acs.jmedchem.7b00115.
Castino, M., Cornish, J., & Clemens, K. (2015). Inhibition of histone deacetylases facilitates extinction and attenuates reinstatement of nicotine self-administration in rats. PLoS One, 10(4), e0124796. https://doi.org/10.1371/journal.pone.0124796.
De Sa Nogueira, D., Merienne, K., & Befort, K. (2019). Neuroepigenetics and addictive behaviors: Where do we stand? Neuroscience & Biobehavioral Reviews, 106, 58–72. https://doi.org/10.1016/j.neubiorev.2018.08.018.
Ferguson, D., Koo, J. W., Feng, J., Heller, E., Rabkin, J., Heshmati, M., et al. (2013). Essential role of SIRT1 signaling in the nucleus accumbens in cocaine and morphine action. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 33(41), 16088–16098. https://doi.org/10.1523/JNEUROSCI.1284-13.2013.
Godino, A., Jayanthi, S., & Cadet, J. L. (2015). Epigenetic landscape of amphetamine and methamphetamine addiction in rodents. Epigenetics, 10(7), 574–580. https://doi.org/10.1080/15592294.2015.1055441.
Gräff, J., & Tsai, L. H. (2013). Histone acetylation: Molecular mnemonics on the chromatin. Nature Reviews Neuroscience, 14(2), 97–111. https://doi.org/10.1038/nrn3427.
Gulyaeva, N. V. (2017). Molecular mechanisms of neuroplasticity: An expanding universe. Biochemistry (Moscow), 82(3), 237–242. https://doi.org/10.1134/S0006297917030014.
He, X. T., Zhou, K. X., Zhao, W. J., Zhang, C., Deng, J. P., Chen, F. M., et al. (2018). Inhibition of histone deacetylases attenuates morphine tolerance and restores MOR expression in the DRG of BCP rats. Frontiers in Pharmacology, 9, 509. https://doi.org/10.3389/fphar.2018.00509.
Hitchcock, L. N., Raybuck, J. D., Wood, M. A., & Lattal, K. M. (2019). Effects of a histone deacetylase 3 inhibitor on extinction and reinstatement of cocaine self-administration in rats. Psychopharmacology, 236(1), 517–529. https://doi.org/10.1007/s00213-018-5122-2.
Jaenisch, R., & Bird, A. (2003). Epigenetic regulation of gene expression: How the genome integrates intrinsic and environmental signals. Nature Genetics, 33(S3), 245–254. https://doi.org/10.1038/ng1089.
Kalivas, P. W., & O’Brien, C. (2008). Drug addiction as a pathology of staged neuroplasticity. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 33(1), 166–180. https://doi.org/10.1038/sj.npp.1301564.
Kelley, A. E., & Berridge, K. C. (2002). The neuroscience of natural rewards: Relevance to addictive drugs. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 22(9), 3306–3311. https://doi.org/10.1523/JNEUROSCI.22-09-03306.2002.
Koob, G. F. (2013). Addiction is a reward deficit and stress surfeit disorder. Frontiers in Psychiatry, 4, 72. https://doi.org/10.3389/fpsyt.2013.00072.
Koob, G. F. (2015). The dark side of emotion: The addiction perspective. European Journal of Pharmacology, 753, 73–87. https://doi.org/10.1016/j.ejphar.2014.11.044.
Koob, G. F., & Schulkin, J. (2019). Addiction and stress: An allostatic view. Neuroscience and Biobehavioral Reviews, 106, 245–262. https://doi.org/10.1016/j.neubiorev.2018.09.008.
Koob, G. F., & Volkow, N. D. (2010). Neurocircuitry of addiction. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 35(1), 217–238. https://doi.org/10.1038/npp.2009.110.
Koob, G. F., & Volkow, N. D. (2016). Neurobiology of addiction: A neurocircuitry analysis. The Lancet Psychiatry, 3(8), 760–773. https://doi.org/10.1016/S2215-0366(16)00104-8.
Kumar, A., Choi, K. H., Renthal, W., Tsankova, N. M., Theobald, D. E., Truong, H. T., et al. (2005). Chromatin remodeling is a key mechanism underlying cocaine-induced plasticity in striatum. Neuron, 48(2), 303–314. https://doi.org/10.1016/j.neuron.2005.09.023.
Lawrence, M., Daujat, S., & Schneider, R. (2016). Lateral thinking: How histone modifications regulate gene expression. Trends in Genetics: TIG, 32(1), 42–56. https://doi.org/10.1016/j.tig.2015.10.007.
Lobo, M. K., Covington, H. E., Chaudhury, D., Friedman, A. K., Sun, H., Damez-Werno, D., et al. (2010). Cell type-specific loss of BDNF signaling mimics optogenetic control of cocaine reward. Science, 330(6002), 385–390. https://doi.org/10.1126/science.1188472.
López-Moreno, J. A., Marcos, M., Calleja-Conde, J., Echeverry-Alzate, V., Bühler, K. M., Costa-Alba, P., et al. (2015). Histone Deacetylase gene expression following binge alcohol consumption in rats and humans. Alcoholism, Clinical and Experimental Research, 39(10), 1939–1950. https://doi.org/10.1111/acer.12850.
Martin, T. A., Jayanthi, S., McCoy, M. T., Brannock, C., Ladenheim, B., Garrett, T., et al. (2012). Methamphetamine causes differential alterations in gene expression and patterns of histone acetylation/hypoacetylation in the rat nucleus accumbens. PLoS One, 7(3), e34236. https://doi.org/10.1371/journal.pone.0034236.
Maze, I., Noh, K. M., Soshnev, A. A., & Allis, C. D. (2014a). Every amino acid matters: Essential contributions of histone variants to mammalian development and disease. Nature Reviews Genetics, 15(4), 259–271. https://doi.org/10.1038/nrg3673.
Maze, I., Shen, L., Zhang, B., Garcia, B., Shao, N., Mitchell, A., et al. (2014b). Analytical tools and current challenges in the modern era of neuroepigenomics. Nature Neuroscience, 17(11), 1476–1490. https://doi.org/10.1038/nn.3816.
Mews, P., Walker, D. M., & Nestler, E. J. (2018). Epigenetic priming in drug addiction. Cold Spring Harbor Symposia on Quantitative Biology, 83, 131–139. https://doi.org/10.1101/sqb.2018.83.037663.
Moonat, S., Sakharkar, A. J., Zhang, H., Tang, L., & Pandey, S. C. (2013). Aberrant histone deacetylase2-mediated histone modifications and synaptic plasticity in the amygdala predisposes to anxiety and alcoholism. Biological Psychiatry, 73(8), 763–773. https://doi.org/10.1016/j.biopsych.2013.01.012.
National Institute on Drug Abuse (NIDA). (2020). Commonly abused drugs charts. Retrieved from https://www.drugabuse.gov/drugs-abuse
Nestler, E. J. (2014). Epigenetic mechanisms of drug addiction. Neuropharmacology, 76, 259–268. https://doi.org/10.1016/j.neuropharm.2013.04.004.
Nestler, E. J., & Lüscher, C. (2019). The molecular basis of drug addiction: Linking epigenetic to synaptic and circuit mechanisms. Neuron, 102(1), 48–59. https://doi.org/10.1016/j.neuron.2019.01.016.
Pandey, S. C., Kyzar, E. J., & Zhang, H. (2017). Epigenetic basis of the dark side of alcohol addiction. Neuropharmacology, 122, 74–84. https://doi.org/10.1016/j.neuropharm.2017.02.002.
Pandey, S. C., Sakharkar, A. J., Tang, L., & Zhang, H. (2015). Potential role of adolescent alcohol exposure-induced amygdaloid histone modifications in anxiety and alcohol intake during adulthood. Neurobiology of Disease, 82, 607–619. https://doi.org/10.1016/j.nbd.2015.03.019.
Pandey, S. C., Ugale, R., Zhang, H., Tang, L., & Prakash, A. (2008). Brain chromatin remodeling: A novel mechanism of alcoholism. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 28(14), 3729–3737. https://doi.org/10.1523/JNEUROSCI.5731-07.2008.
Pascual, M., Do Couto, B. R., Alfonso-Loeches, S., Aguilar, M. A., Rodriguez-Arias, M., & Guerri, C. (2012). Changes in histone acetylation in the prefrontal cortex of ethanol-exposed adolescent rats are associated with ethanol-induced place conditioning. Neuropharmacology, 62(7), 2309–2319. https://doi.org/10.1016/j.neuropharm.2012.01.011.
Ron, D., & Barak, S. (2016). Molecular mechanisms underlying alcohol-drinking behaviours. Nature Reviews Neuroscience, 17(9), 576–591. https://doi.org/10.1038/nrn.2016.85.
Sadakierska-Chudy, A., Frankowska, M., Jastrzębska, J., Wydra, K., Miszkiel, J., Sanak, M., & Filip, M. (2017). Cocaine administration and its withdrawal enhance the expression of genes encoding histone-modifying enzymes and histone acetylation in the rat prefrontal cortex. Neurotoxicity Research, 32(1), 141–150. https://doi.org/10.1007/s12640-017-9728-7.
Sakharkar, A. J., Tang, L., Zhang, H., Chen, Y., Grayson, D. R., & Pandey, S. C. (2014). Effects of acute ethanol exposure on anxiety measures and epigenetic modifiers in the extended amygdala of adolescent rats. The International Journal of Neuropsychopharmacology, 17(12), 2057–2067. https://doi.org/10.1017/S1461145714001047.
Seo, D., & Sinha, R. (2015). Neuroplasticity and predictors of alcohol recovery. Alcohol Research: Current Reviews, 37(1), 143–152.
United Nations Office on Drugs and Crime (UNODC). (2019). World drug report 2019. Retrieved from https://wdr.unodc.org/wdr2019/
Volkow, N. D., & Morales, M. (2015). The brain on drugs: From reward to addiction. Cell, 162(4), 712–725. https://doi.org/10.1016/j.cell.2015.07.046.
Wang, L., Lv, Z., Hu, Z., Sheng, J., Hui, B., Sun, J., & Ma, L. (2010). Chronic cocaine-induced H3 acetylation and transcriptional activation of CaMKIIα in the nucleus accumbens is critical for motivation for drug reinforcement. Neuropsychopharmacology, 35(4), 913–928. https://doi.org/10.1038/npp.2009.193.
Warnault, V., Darcq, E., Levine, A., Barak, S., & Ron, D. (2013). Chromatin remodeling--a novel strategy to control excessive alcohol drinking. Translational Psychiatry, 3(2), e231. https://doi.org/10.1038/tp.2013.4.
Wise, R. A. (2008). Dopamine and reward: The anhedonia hypothesis 30 years on. Neurotoxicity Research, 14(2–3), 169–183. https://doi.org/10.1007/BF03033808.
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de Carvalho, L.M. (2021). Neuroscience, Epigenetics, and Psychotropic Substances. In: De Micheli, D., Andrade, A.L.M., Reichert, R.A., Silva, E.A.d., Pinheiro, B.d.O., Lopes, F.M. (eds) Drugs and Human Behavior. Springer, Cham. https://doi.org/10.1007/978-3-030-62855-0_7
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