Gene Expression Survey of Serotonin Receptors (5HTR2A and 5HTR3A) and Monoamine Oxidases Enzyme After Treatment With Methadone in Addicted Individuals
International Journal of Medical Toxicology and Forensic Medicine,
Vol. 9 No. 3 (2019),
1 July 2019
,
Page 125-132
https://doi.org/10.32598/ijmtfm.v9i3.25480
Abstract
Background: Addiction disrupts the nervous system of the reward system, stimulus, and memory in the brain. The disruption of these systems in the brain causes biological, physiological, social, and psychological complications. Addiction is considered a psychological, social, and economic disorder in terms of medicine, psychology, and sociology, as well as philosophy, law, ethics, and religion. The most important place of narcotic effect is the brain, and receptors affect these substances. Dopamine and serotonin receptors are among the most important receptors, in which drugs affect them. Methadone is also an opiate drug that is even more addictive than morphine and heroin and is often used as a preservative to control heroin and narcotic addiction.
Methods: In this study, 3 genes of 5-Hydroxytryptamine Receptor 2 A (5HT2Ra), 5-Hydroxytryptamine Receptor 3 A (5HT3Ra), and Monoamine Oxidases A (MAOA), which play an important role in serotonin function, were examined in Peripheral Blood Mononuclear Cells (PBMCs) of heroin addicts, who had been quitting addiction with methadone for 3 months. Therefore, peripheral blood PBMCs were isolated. cDNA was synthesized from mRNA; then, the expression of the gene was measured by real-time Polymerase Chain Reaction (PCR).
Results: The expression of MAOA gene in the PBMCs of the addicted patients with methadone was significantly reduced compared to the control group, while the expression of 5HT2Ra and 5HT3Ra genes showed no change in the two groups.
Conclusion: These results suggest that Methadone Maintenance Treatment (MMT) may be moderated by 5HT2Ra and 5 HT3Ra serotonin receptors and returned to their previous efficacy, but MAOA was significantly reduced.
- Addiction
- Heroin
- Types of serotonin
- Enzyme MAOA
- Methadone
- MMT
How to Cite
References
Volkow ND, Morales M. The brain on drugs: From reward to addiction. Journal of Cell. 2015; 162(4):712-25. [DOI:10.1016/j.cell.2015.07.046] [PMID]
Nestler EJ. Cellular basis of memory for addiction. Dialogues in Clinical Neuroscience. 2013; 15(4):431-43. [PMID] [PMCID]
Vassoler FM, Sadri-Vakili G. Mechanisms of transgenerational inheritance of addictive-like behaviors. Neuroscience. 2014; 264:198-206. [DOI:10.1016/j.neuroscience.2013.07.064] [PMID] [PMCID]
Kirby LG, Zeeb FD, Winstanley CA. Contributions of serotonin in addiction vulnerability. Neuropharmacology. 2011; 61(3):421-32. [DOI:10.1016/j.neuropharm.2011.03.022] [PMID] [PMCID]
Dankoski EC, Wightman RM. Mark Wightman. Monitoring serotonin signaling on a sub second time scale. Frontiers in Integrative Neuroscience. 2013; 7:44. [DOI:10.3389/fnint.2013.00044] [PMID] [PMCID]
Idzko M, Panther E, Stratz C, Müller T, Bayer H, Zissel G, et al. The serotoninergic receptors of human dendritic cells: Identification and coupling to cytokine release. Journal of Immunology (Baltimore). 2004; 172(10):6011-9. [DOI:10.4049/jimmunol.172.10.6011] [PMID]
Sikander A, Rana SV, Prasad KK. Role of serotonin in gastrointestinal motility and irritable bowel syndrome. Clinica Chimica Acta; International Journal of Clinical Chemistry. 2009; 403 (1-2):47-55. [DOI:10.1016/j.cca.2009.01.028] [PMID]
Murphy DL, Andrews AM, Wichems CH, Li Q, Tohda M, Greenberg B. Brain serotonin neurotransmission: An overview and update with an emphasis on serotonin subsystem heterogeneity, multiple receptors, interactions with other neurotransmitter systems, and consequent implications for understanding the actions of serotonergic drugs. The Journal of Clinical Psychiatry. 1998; 59(suppl. 15):4-12. [PMID]
Martin AM, Young RL, Leong L, Rogers GB, Spencer NJ, Jessup CF, et al. The diverse metabolic roles of peripheral serotonin. Endocrinology. 2017; 158(5):1049-63. [DOI:10.1210/en.2016-1839] [PMID]
Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, et al. Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science (New York). 2003; 301(5631):386-9. [DOI:10.1126/science.1083968] [PMID]
Wang RY, Chen HJ, Huang CL, Wang JY, Lee TE, Lee HY, et al. Impacts of GRIN3A, GRM6 and TPH2 genetic polymorphisms on quality of life in methadone maintenance therapy population. PLoS One. 2018; 13(7):e0201408. [DOI:10.1371/journal.pone.0201408] [PMID] [PMCID]
Arreola R, Becerril-Villanueva E, Cruz-Fuentes C, Velasco-Velázquez MA, Garcés-Alvarez ME, Hurtado-Alvarado G, et al. Immunomodulatory effects mediated by serotonin. Journal of Immunology Research. 354957. [DOI:10.1155/2015/354957] [PMID] [PMCID]
Hannon J, Hoyer D. Molecular biology of 5-HT receptors. Behavioural Brain Research. 2008; 195(1):198-213. [DOI:10.1016/j.bbr.2008.03.020] [PMID]
Johnson RE, Chutuape MA, Strain EC, Walsh SL, Stitzer ML, Bigelow GE. A comparison of levomethadyl acetate, buprenorphine, and methadone for opioid dependence. The New England Journal of Medicine. 2000; 343(18):1290-7. [DOI:10.1056/NEJM200011023431802] [PMID]
Oreland L. Platelet monoamine oxidase, personality and alcoholism: The rise, fall and resurrection. Neurotoxicology. 2004; 25(1-2):79-89. [DOI:10.1016/S0161-813X(03)00115-3]
Sunilkumar MM, Lockman K. Practical pharmacology of methadone: A long-acting opioid. Indian Journal of Palliative Care. 24(suppl. 1):S10-14. [DOI:10.4103/IJPC.IJPC_180_17] [PMID] [PMCID]
Weber L. How does methadone work? [Internet]. 2012 [Updated 2018 October 13]. Available from: https://prescription-drug.addictionblog.org/how-does-methadone-work/
Kreek MJ. Methadone-related opioid agonist pharmacotherapy for heroin addiction. History, recent molecular and neurochemical research and future in mainstream medicine. Annals of the New York Academy of Sciences. 2000; 909:186-216. [DOI:10.1111/j.1749-6632.2000.tb06683.x] [PMID]
Gould TJ. Addiction and cognition addict. Addiction science & clinical practice. 2010; 5(2):4-14. [PMID] [PMCID]
Ruffle JK. Molecular neurobiology of addiction: What’s all the (Δ) FosB about? The American Journal of Drug and Alcohol Abuse. 2014; 40(6):428-37. [DOI:10.3109/00952990.2014.933840] [PMID]
Dole VP. Implications of methadone maintenance for theories of narcotic addiction. The Journal of the American Medical Association. 1988; 260(20):3025-9. [DOI:10.1001/jama.260.20.3025] [PMID]
Hartel DM, Schoenbaum EE, Selwyn PA, Kline J, Davenny K, Klein RS, et al. Heroin use during methadone maintenance treatment: The importance of methadone dose and cocaine use. American Journal of Public Health. 1995; 85(1):83-8. [DOI:10.2105/AJPH.85.1.83] [PMID] [PMCID]
Mück-Seler D, Pivac N. Serotonin. Periodicum Biologorum Universal Decimal Classification. 113(1):29-41.
Hapfelmeier G, Tredt C, Haseneder W, B. Eisensamer, Rupprecht R, Rammes G. Co-expression of the 5-HT3B serotonin receptor subunit alters the biophysics of the 5-ht3 receptor. Biophysical Journal. 84(3):1720-33. [DOI:10.1016/S0006-3495(03)74980-7]
Buddy T. Brain Recovery After Stopping Methamphetamine [Internet]. 2019 [Updated 2019 july 25]. Available from: https://www.verywellmind.com/brain-recovery-possible-for-meth-users-67583
Gough B, Ali SF, Slikker WJ, Holson RR. Acute effects of 3,4-methylenedioxymethamphetamine (MDMA) on monoamines in rat caudate. Pharmacology Biochemistry and Behavior. 1991; 39(3):619-23. [DOI:10.1016/0091-3057(91)90137-Q]
Schmidt CJ, Levin JA, Lovenberg W. In vitro and in vivo neurochemical effects of methylenedioxymethamphetamine on striatal monoaminergic systems in the rat brain. Biochemical Pharmacology. 1987; 36(5):747-55. [DOI:10.1016/0006-2952(87)90729-5]
Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, et al. Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse. 2001; 39(1):32-41. [DOI:10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3]
Sabol KE, Seiden LS. Reserpine attenuates D-amphetamine and MDMA-induced transmitter release in vivo: A consideration of dose, core temperature and dopamine synthesis. Brain Research. 1998; 806(1):69-78. [DOI:10.1016/S0006-8993(98)00720-3]
National Institute on Drug Abuse. MDMA (Ecstasy/Molly). 2018 [Updated 2018 June]. Available from: https://www.drugabuse.gov/publications/drugfacts/mdma-ecstasymolly
Bolla KI, McCann UD, Ricaurte GA. Memory impairment in abstinent MDMA (“Ecstasy”) users. Neurology. 1998; 51(6):1532-7. [DOI:10.1212/WNL.51.6.1532] [PMID]
Kish SJ, Furukawa Y, Ang L, Vorce SP and Kalasinsky KS. Striatal serotonin is depleted in brain of a human MDMA (Ecstasy) user. Neurology. 2000; 55(2):294-6. [DOI:10.1212/WNL.55.2.294] [PMID]
Green AR, Mechan AO, Elliott JM, O’Shea E, Colado MI. The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”). Pharmacological Reviews. 2003; 55(3):463-508. [DOI:10.1124/pr.55.3.3] [PMID]
Rudnick G, Wall SC. The molecular mechanism of “ecstasy” (3,4-methylenedioxy-methamphetamine (MDMA)): Serotonin transporters are targets for MDMA-induced serotonin release. Proceedings of the National Academy of Sciences of the United States. 1992; 89(5):1817-21. [DOI:10.1073/pnas.89.5.1817] [PMID] [PMCID]
Thomasius R, Zapletalova P, Petersen K, Buchert R, Andresen B, Wartberg L, et al. Mood, cognition and serotonin transporter availability in current and former ecstasy (MDMA) users: The longitudinal perspective. Journal of Psychopharmacology (Oxford, England). 2006; 20(2):211-25. [DOI:10.1177/0269881106059486] [PMID]
Daubert EA, Heffron DS, Mandell JW, Condron BG. Serotonergic dystrophy induced by excess serotonin. Molecular and Cellular Neuroscience. 2010; 44(3):297-306. [DOI:10.1016/j.mcn.2010.04.001] [PMID] [PMCID]
American Addiction Centers. Drug Abuse and Chemical Imbalance in the Brain: Dopamine, Serotonin & More [Internet]. 2018 [Updated 2019 June 17]. Available from: https://americanaddictioncenters.org/health-complications-addiction/chemical-imbalance
Joseph H, Stancliff S, Langrod J. Methadone Maintenance Treatment (MMT): A review of historical and clinical issues. Mount Sinai Journal of Medicine. 2000; 67(5-6):347-64. [PMID]
Sun Y, Liu L, Feng J, Yue W, Lu L, Fan Y, et al. MAOA rs1137070 and heroin addiction interactively alter gray matter volume of the salience network. Scientific Reports. 2017; 7:45321. [DOI:10.1038/srep45321] [PMID] [PMCID]
Martinez TT, Martinez DN. A case of serotonin syndrome associated with methadone overdose. Proceedings of the Western Pharmacology Society. 2008; 51:42-4. [PMID]
Rastogi R, Swarm RA, Patel TA. Case scenario: Opioid association with serotonin syndrome: Implications to the practitioners. Anesthesiology. 2011; 115(6):1291-8. [DOI:10.1097/ALN.0b013e31823940c0] [PMID]
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