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.
Nora D.Volkow and Marisela Morales (2015). The Brain on Drugs: From Reward to Addiction. Journal of Cell. 162, 4, 13, 712-725
Nestler EJ. (2013). "Cellular basis of memory for addiction". Dialogues Clin. Neurosci. 15 (4): 431–443.
Vassoler FM and Sadri-Vakili G. (2014). "Mechanisms of transgenerational inheritance of addictive-like behaviors". Neuroscience. 264: 198–206.
https://www.eghtesadonline.com/n/1Q19 , Iran Drug Control Headquarters 2017
LG Kirby, FD Zeeb, and CA Winstanley. (2011) Contributions of Serotonin in Addiction Vulnerability. Neuropharmacology. 61(3): 421–432.
Elyse C. Dankoski and R. Mark Wightman. (2013). Monitoring serotonin signaling on a sub second time scale. Front Integr Neurosci. 7: 44.
Marco Idzko, Elisabeth Panther, Christian Stratz, Tobias Müller, Hannes Bayer, Gernot Zissel, Thorsten Dürk, Stephan Sorichter, Francesco Di Virgilio, M ichael Geissler, Bernd Fiebich, Yared Herouy, Peter Elsner, Johannes Norgauer and Davide Ferrari. (2004). the Serotoninergic Receptors of Human Dendritic Cells: Identification and Coupling to Cytokine Release, J Immunol, 172 (10) 6011-6019
Sikander A, Rana SV and Prasad KK. (2009). Role of serotonin in gastrointestinal motility and irritable bowel syndrome. Clin Chim Acta.403 (1-2):47-55.
Murphy DL, Andrews AM, Wichems CH, Li Q, Tohda M, Greenberg and B. Brain. (1998). 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. J Clin Psychiatry.; 59 Suppl 15:412.
Alyce M. Martin Richard L. Young Lex Leong Geraint B. Rogers Nick J. Spencer Claire F. Jessup Damien and J. Keating. (2017). the Diverse Metabolic Roles of Peripheral Serotonin. Endocrinology, Volume 158, Issue 5, Pages 1049–1063
Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R. (2003). Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science. 18; 301(5631):386-9.
Ruey-Yun Wang, Hsiu-Ju Chen, Chieh-Liang Huang, Jiun-Yi Wang, Tsui-Er Lee, Hsiang-Yen Lee and Chin-Chuan Hung. (2018). Impacts of GRIN3A, GRM6 and TPH2 genetic polymorphisms on quality of life in methadone maintenance therapy population. https://doi.org/10.1371/journal.pone.0201408
Rodrigo Arreola, Enrique Becerril-Villanueva, Carlos Cruz-Fuentes, Marco Antonio Velasco-Velázquez, María Eugenia Garcés-Alvarez, Gabriela Hurtado-Alvarado, Saray Quintero-Fabian, and Lenin Pavón.(2015). Immunomodulatory Effects Mediated by Serotonin. J Immunol Res: 354957.
Hannon J and Hoyer D. (2008). Molecular biology of 5-HT receptors. Behav Brain Res. 16; 195(1):198-213
Johnson RE, Chutuape MA, Strain EC, Walsh SL, Stitzer ML and Bigelow GE. (2000). A comparison of levomethadyl acetate, buprenorphine, and methadone for opioid dependence. N Engl J Med. 2; 343(18):1290-7.
Oreland L. (2004). Platelet monoamine oxidase, personality and alcoholism: the rise, fall and resurrection. Neurotoxicology. 25(1-2):79-89.
MM Sunilkumar and Kashelle Lockman. (2018). Practical Pharmacology of Methadone: A Long-acting Opioid. Indian J Palliat Care. 24(Suppl 1): S10–S14.
Kreek MJ. (2000). Methadone-related opioid agonist pharmacotherapy for heroin addiction. History, recent molecular and neurochemical research and future in mainstream medicine. Ann N Y Acad Sci.; 909:186-216.
Thomas J. Gould. (2010). Addiction and Cognition Addict. Sci Clin Pract. 5(2): 4–14.
Eric J. Nestler. (2013). Cellular basis of memory for addiction. Dialogues Clin Neurosci. 15(4): 431–443.
Ruffle JK. (2014). Molecular neurobiology of addiction: what's all the (Δ) FosB about? Am J Drug Alcohol Abuse. 40(6):428-37.
Dole VP. (1988). Implications of methadone maintenance for theories of narcotic addiction. JAMA. 25; 260(20):3025-9.
D M Hartel, E Schoenbaum, P A Selwyn, J Kline, K Davenny, R S Klein, and G H Friedland. (1995). Heroin use during methadone maintenance treatment: the importance of methadone dose and cocaine use. Am J Public Health. 85(1): 83–88.
MM Sunilkumar and Kashelle Lockman. (2018). Practical Pharmacology of Methadone: A Long-acting Opioid. Indian J Palliat Care. Jan; 24(Suppl 1): S10–S14.
Johnson RE, Chutuape MA, Strain EC, Walsh SL, Stitzer ML and Bigelow GE. (2000). A comparison of levomethadyl acetate, buprenorphine, and methadone for opioid dependence. N Engl J Med. 2; 343(18):1290-7
DOROTEA MÜCK-SELER and NELA PIVAC. (2011). Serotonin. PERIODICUM BIOLOGORUM UDC 57:61.VOL. 113, No 1, 29–41.
G. Hapfelmeier, C. Tredt, R. Haseneder, W. Zieglgänsberger, B. Eisensamer, R. Rupprecht, and G. Rammes. (2003). Co-expression of the 5-HT3B Serotonin Receptor Subunit Alters the Biophysics of the 5-HT3 Receptor. Biophys J. 84(3): 1720–1733.
Gough B, Ali SF, Slikker W Jr and Holson RR. (1991). Acute effects of 3, 4-methylenedioxymethamphetamine (MDMA) on monoamines in rat caudate. Pharmacol Biochem Behav. 39(3):619-23.
Schmidt CJ, Levin JA and Lovenberg W. (1987). In vitro and in vivo neurochemical effects of methylenedioxymethamphetamine on striatal monoaminergic systems in the rat brain. Biochem Pharmacol. 1; 36(5):747-55.
Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI and Partilla JS. (2001). Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse. 39(1):32-41.
Sabol KE and Seiden LS. (1998). Reserpine attenuates D-amphetamine and MDMA-induced transmitter release in vivo: a consideration of dose, core temperature and dopamine synthesis. Brain Res. 21; 806(1):69-78.
Bolla KI, McCann UD and Ricaurte GA. (1998). Memory impairment in abstinent MDMA ("Ecstasy") users. Neurology.51 (6):1532-7.
Kish SJ, Furukawa Y, Ang L, Vorce SP and Kalasinsky KS. (2000).Striatal serotonin is depleted in brain of a human MDMA (Ecstasy) user. Neurology. 25; 55(2):294-6.
Green AR, Mechan AO, Elliott JM, O'Shea E and Colado MI. (2003). The pharmacology and clinical pharmacology of 3,4methylenedioxymethamphetamine (MDMA, "ecstasy"). Pharmacol Rev. 55(3):463-508.
Rudnick G and Wall SC. (1992). The molecular mechanism of "ecstasy" [3, 4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Proc Natl Acad Sci U S A. 1; 89(5):1817-21.
Thomasius R, Zapletalova P, Petersen K, Buchert R, Andresen B, Wartberg L, Nebeling B and Schmoldt A. (2006). Mood, cognition and serotonin transporter availability in current and former ecstasy (MDMA) users: the longitudinal perspective. J Psychopharmacol.20 (2):211-25.
Elizabeth A. Daubert, Daniel S. Heffron, James W. Mandell and Barry G Condron. (2010). Serotonergic dystrophy induced by excess serotonin. Molecular and Cellular Neuroscience 44: 297–306.
https: //americanaddictioncenters.org/health-complications-addiction/chemical-imbalance. (2018).
https: //www.verywellmind.com/brain-recovery-possible-for-meth-users-67583. (2018).
Joseph H, Stancliff S and Langrod J. (2000). Methadone maintenance treatment (MMT): a review of historical and clinical issues. Mt Sinai J Med. 67(5-6):347-64.
Yan Sun, Linwen Liu, Jiajia Feng, Weihua Yue, Lin Lu, Yong Fan and Jie Shi. (2017). MAOA rs1137070 and heroin addiction interactively alter gray matter volume of the salience network. J Scientific Reports. 7:45321
Martinez TT and Martinez DN. (2008). A case of serotonin syndrome associated with methadone overdose. Proc West Pharmacol Soc.; 51:42-4.
Rastogi R, Swarm RA and Patel TA. (2011). Case scenario: opioid association with serotonin syndrome: implications to the practitioners. Anesthesiology. 115(6):1291-8.