Epigenetic Effects of Addictive Drugs in the Nucleus Accumbens

Overview

Journal Front Mol Neurosci

Specialty Molecular Biology

Date 2022 Jul 11

PMID 35813068

Authors

Ethan M Anderson

Makoto Taniguchi

Affiliations

Soon will be listed here.

Abstract

Substance use induces long-lasting behavioral changes and drug craving. Increasing evidence suggests that epigenetic gene regulation contributes to the development and expression of these long-lasting behavioral alterations. Here we systematically review extensive evidence from rodent models of drug-induced changes in epigenetic regulation and epigenetic regulator proteins. We focus on histone acetylation and histone methylation in a brain region important for drug-related behaviors: the nucleus accumbens. We also discuss how experimentally altering these epigenetic regulators via systemically administered compounds or nucleus accumbens-specific manipulations demonstrate the importance of these proteins in the behavioral effects of drugs and suggest potential therapeutic value to treat people with substance use disorder. Finally, we discuss limitations and future directions for the field of epigenetic studies in the behavioral effects of addictive drugs and suggest how to use these insights to develop efficacious treatments.

Citing Articles

Epigenetic drugs and psychedelics as emerging therapies for alcohol use disorder: insights from preclinical studies.

Hilal F, Jeanblanc J, Deschamps C, Naassila M, Pierrefiche O, Ben Hamida S J Neural Transm (Vienna). 2024; 131(5):525-561.

PMID: 38554193 DOI: 10.1007/s00702-024-02757-3.

Histone modifications in cocaine, methamphetamine and opioids.

Cheng J, He Z, Chen Q, Lin J, Peng Y, Zhang J Heliyon. 2023; 9(6):e16407.

PMID: 37265630 PMC: 10230207. DOI: 10.1016/j.heliyon.2023.e16407.

Convergent actions of stress and stimulants via epigenetic regulation of neural circuitry.

Murphy M, Heller E Trends Neurosci. 2022; 45(12):955-967.

PMID: 36280459 PMC: 9671852. DOI: 10.1016/j.tins.2022.10.001.

References

Yang X . Lysine acetylation and the bromodomain: a new partnership for signaling. Bioessays. 2004; 26(10):1076-87. DOI: 10.1002/bies.20104. View

Sheng J, Lv Z, Wang L, Zhou Y, Hui B . Histone H3 phosphoacetylation is critical for heroin-induced place preference. Neuroreport. 2011; 22(12):575-80. DOI: 10.1097/WNR.0b013e328348e6aa. View

Carullo N, Phillips Iii R, Simon R, Roman Soto S, Hinds J, Salisbury A . Enhancer RNAs predict enhancer-gene regulatory links and are critical for enhancer function in neuronal systems. Nucleic Acids Res. 2020; 48(17):9550-9570. PMC: 7515708. DOI: 10.1093/nar/gkaa671. View

Host L, Anglard P, Romieu P, Thibault C, Dembele D, Aunis D . Inhibition of histone deacetylases in rats self-administering cocaine regulates lissencephaly gene-1 and reelin gene expression, as revealed by microarray technique. J Neurochem. 2010; 113(1):236-47. DOI: 10.1111/j.1471-4159.2010.06591.x. View

Caputi F, Palmisano M, Carboni L, Candeletti S, Romualdi P . Opioid gene expression changes and post-translational histone modifications at promoter regions in the rat nucleus accumbens after acute and repeated 3,4-methylenedioxy-methamphetamine (MDMA) exposure. Pharmacol Res. 2016; 114:209-218. DOI: 10.1016/j.phrs.2016.10.023. View

Deng J, Rodriguiz R, Hutchinson A, Kim I, Wetsel W, West A . MeCP2 in the nucleus accumbens contributes to neural and behavioral responses to psychostimulants. Nat Neurosci. 2010; 13(9):1128-36. PMC: 2928851. DOI: 10.1038/nn.2614. View

Ikegami D, Narita M, Imai S, Miyashita K, Tamura R, Narita M . Epigenetic modulation at the CCR2 gene correlates with the maintenance of behavioral sensitization to methamphetamine. Addict Biol. 2010; 15(3):358-61. DOI: 10.1111/j.1369-1600.2010.00219.x. View

Tomasiewicz H, Jacobs M, Wilkinson M, Wilson S, Nestler E, Hurd Y . Proenkephalin mediates the enduring effects of adolescent cannabis exposure associated with adult opiate vulnerability. Biol Psychiatry. 2012; 72(10):803-10. PMC: 3440551. DOI: 10.1016/j.biopsych.2012.04.026. View

Zhang X, Huang Y, Shi X . Emerging roles of lysine methylation on non-histone proteins. Cell Mol Life Sci. 2015; 72(22):4257-72. PMC: 11114002. DOI: 10.1007/s00018-015-2001-4. View

10.

Campbell R, Kramar E, Pham L, Beardwood J, Augustynski A, Lopez A . HDAC3 Activity within the Nucleus Accumbens Regulates Cocaine-Induced Plasticity and Behavior in a Cell-Type-Specific Manner. J Neurosci. 2021; 41(13):2814-2827. PMC: 8018887. DOI: 10.1523/JNEUROSCI.2829-20.2021. View

11.

Cates H, Li X, Purushothaman I, Kennedy P, Shen L, Shaham Y . Genome-wide transcriptional profiling of central amygdala and orbitofrontal cortex during incubation of methamphetamine craving. Neuropsychopharmacology. 2018; 43(12):2426-2434. PMC: 6180053. DOI: 10.1038/s41386-018-0158-x. View

12.

Wang L, Lv Z, Hu Z, Sheng J, Hui B, Sun J . Chronic cocaine-induced H3 acetylation and transcriptional activation of CaMKIIalpha in the nucleus accumbens is critical for motivation for drug reinforcement. Neuropsychopharmacology. 2009; 35(4):913-28. PMC: 3055366. DOI: 10.1038/npp.2009.193. View

13.

Anderson E, Sun H, Guzman D, Taniguchi M, Cowan C, Maze I . Knockdown of the histone di-methyltransferase G9a in nucleus accumbens shell decreases cocaine self-administration, stress-induced reinstatement, and anxiety. Neuropsychopharmacology. 2018; 44(8):1370-1376. PMC: 6785019. DOI: 10.1038/s41386-018-0305-4. View

14.

Pascoli V, Turiault M, Luscher C . Reversal of cocaine-evoked synaptic potentiation resets drug-induced adaptive behaviour. Nature. 2011; 481(7379):71-5. DOI: 10.1038/nature10709. View

15.

Rotllant D, Armario A . Brain pattern of histone H3 phosphorylation after acute amphetamine administration: its relationship to brain c-fos induction is strongly dependent on the particular brain area. Neuropharmacology. 2011; 62(2):1073-81. DOI: 10.1016/j.neuropharm.2011.10.019. View

16.

Seth P, Scholl L, Rudd R, Bacon S . Overdose Deaths Involving Opioids, Cocaine, and Psychostimulants - United States, 2015-2016. MMWR Morb Mortal Wkly Rep. 2018; 67(12):349-358. PMC: 5877356. DOI: 10.15585/mmwr.mm6712a1. View

17.

Pastor V, Host L, Zwiller J, Bernabeu R . Histone deacetylase inhibition decreases preference without affecting aversion for nicotine. J Neurochem. 2010; 116(4):636-45. DOI: 10.1111/j.1471-4159.2010.07149.x. View

18.

Hitchcock L, Raybuck J, Wood M, Lattal K . Effects of a histone deacetylase 3 inhibitor on extinction and reinstatement of cocaine self-administration in rats. Psychopharmacology (Berl). 2018; 236(1):517-529. PMC: 6459190. DOI: 10.1007/s00213-018-5122-2. View

19.

Johnstone A, Andrade N, Barbier E, Khomtchouk B, Rienas C, Lowe K . Dysregulation of the histone demethylase KDM6B in alcohol dependence is associated with epigenetic regulation of inflammatory signaling pathways. Addict Biol. 2019; 26(1):e12816. PMC: 7757263. DOI: 10.1111/adb.12816. View

20.

Anderson E, Wissman A, Chemplanikal J, Buzin N, Guzman D, Larson E . BDNF-TrkB controls cocaine-induced dendritic spines in rodent nucleus accumbens dissociated from increases in addictive behaviors. Proc Natl Acad Sci U S A. 2017; 114(35):9469-9474. PMC: 5584417. DOI: 10.1073/pnas.1702441114. View