Fatin H. Zakaria, Samhani Ismail, Khadijah N.M.J
Fatin H. Zakaria1, Samhani Ismail2*, Khadijah N.M.J2
1Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia Health Campus, 16150, Kubang Kerian, Kota Bharu, Kelantan, Malaysia.
2Faculty of Medicine, Universiti Sultan Zainal Abidin (UniSZA) Medical Campus, 20400 Jalan Sultan Mahmud, Kuala Terengganu, Terengganu, Malaysia.
Volume - 15,
Issue - 8,
Year - 2022
A persistent 3,4-Methylenedioxymethamphetamine (MDMA) exposure may disrupt the human body serotonergic system which subsequently leads to physical and psychiatric chaos. Serotonin, a well-known monoamine neurotransmitter which is the main target of MDMA can be found in cerebrospinal (CSF) fluid. Its variation reflects the severity of neuronal damage caused by MDMA exposure. Hence, this article aimed to review the potential of serotonin as biomarker for neuronal damage posed by MDMA. Articles from main databases including PubMed, Scopus and Web of Science were analysed and its information about serotonin variation in cerebrospinal fluid in response to MDMA exposure were extracted. MDMA is affine to serotonergic system, and can represents as a change in the level of serotonin in the CSF. It provides critical information about underlying mechanisms of neuronal damage from neurotoxicity, neurodegenerative process, excitotoxicity and hallucination due to MDMA exposure. Since serotonin variation in the CSF reflects the severity of neuronal damages, serotonin is potentially be used as an early indicator to assess neural injury caused by MDMA that plays an important role in intervention purpose. Serotonin variation in the CSF reflects the severity of neuronal damages. Its variation in CSF can be used as a biomarker for assessing neuronal damage following MDMA exposure.
Cite this article:
Fatin H. Zakaria, Samhani Ismail, Khadijah N.M.J. Cerebrospinal Fluid Serotonin level as Biomarker for Neurotoxicity after 3,4-Methylenedioxymethamphetamine (MDMA). Research Journal of Pharmacy and Technology. 2022; 15(8):3796-1. doi: 10.52711/0974-360X.2022.00637
Fatin H. Zakaria, Samhani Ismail, Khadijah N.M.J. Cerebrospinal Fluid Serotonin level as Biomarker for Neurotoxicity after 3,4-Methylenedioxymethamphetamine (MDMA). Research Journal of Pharmacy and Technology. 2022; 15(8):3796-1. doi: 10.52711/0974-360X.2022.00637 Available on: https://rjptonline.org/AbstractView.aspx?PID=2022-15-8-79
1. Xie T, Tong L, McLane MW, Hatzidimitriou G, Yuan J, McCann U and Ricaurte G. Loss of serotonin transporter protein after MDMA and other ring-substituted amphetamines. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 2006;31(12):2639–2651. https://doi.org/10.1038/sj.npp.1301031
2. Figurasin R and Maguire NJ. 3,4-Methylenedioxy-Methamphetamine (MDMA, Ecstacy, Molly) Toxicity. Treasure Island (FL): Stat Pearls Publishing, 2019.
3. Strote J, Lee JE and Wechsler H. Increasing MDMA use among college students: Results of a national survey. Journal of Adolescent Health, 2002;30(1):64–72. https://doi.org/10.1016/S1054-139X(01)00315-9
4. Adell A, Bortolozzi A, Díaz-Mataix L, Santana N, Celada P, and Artigas F. .8-Serotonin Interaction with Other Transmitter Systems. Handbook of Behavioral Neuroscience, 2010; 21: 259-276.
5. Meyer JS. 3,4-methylenedioxymethamphetamine (MDMA): current perspectives. Substance Abuse and Rehabilitation 2013:4, 83-99. http://dx.doi.org/10.2147/SAR.S37258.
6. Puig MV, and Gulledge AT. Serotonin and Prefrontal Cortex Function: Neurons, Networks and Circuits. Molecular Neurobiology, 2011;44(3):1–16. https://doi.org/10.1007/s12035-011-8214-0
7. Seiden LS, Lew R and Malberg JE. Neurotoxicity of methamphetamine and methylenedioxymethamphetamine. Neurotoxicity research, 2001;3(1):101-116.
8. O’Hearn E, Battaglia G, De Souza EB, Kuhar MJ and Molliver ME. Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity. The Journal of Neuroscience : The Official Journal of the Society for Neuroscience, 1988;8(8):2788–803. Retrieved from. http://www.jneurosci.org/content/8/8/2788.abstract
9. Yamamoto S, Morinobu S, Fuchikami M, Kurata A, Kozuru T and Yamawaki S. Effects of single prolonged stress and D-cycloserine on contextual fear extinction and hippocampal NMDA receptor expression in a rat model of PTSD. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 2008;33(9):2108–2116. https://doi.org/10.1038/sj.npp.1301605
10. Gouzoulis-mayfrank E and Daumann J. Translational research, 2009; 305–317.
11. Ma Z, Rudacille M, Prentice HM and Tao R. Characterization of electroencephalographic and biochemical responses at 5-HT promoting drug-induced onset of serotonin syndrome in rats. Journal of Neurochemistry, 2013;125(5):774–789. https://doi.org/10.1111/jnc.12141
12. Cadet JL, Krasnova IN, Jayanthi S and Lyles J. Neurotoxicity of substituted amphetamines: Molecular and cellular mechanisms. Neurotoxicity Research, 2007;11(3–4):183–202. https://doi.org/10.1007/BF03033567
13. Degenhardt L and Hall W (eds). The health and psychological effects of “ecstasy” (MDMA) use. National Drug and Alcohol Research Centre. University of New South Wales, Sydney. NDARC Monograph, 2010; 62.
14. Gudelsky GA and Nash JF. Carrier‐Mediated Release of Serotonin by 3, 4‐Methylenedioxymethamphetamine: Implications for Serotonin‐Dopamine Interactions. Journal of Neurochemistry, 1996;66(1):243-249.
15. Crespi D, Mennini T and Gobbi M. Carrier‐dependent and Ca2+‐dependent 5‐HT and dopamine release induced by (+)‐amphetamine, 3,4‐methylendioxy‐methamphetamine, p‐chloroamphetamine and (+)‐fenfluramine. British journal of pharmacology, 1997;121(8):1735-1743.
16. Kalant H. The pharmacology and toxicology of “ecstasy”(MDMA) and related drugs. Canadian Medical Association Journal, 2001;165(7):917–928. https://doi.org/10.1111/j.1476- 5381.2012.02065.x
17. Rothman RB and Baumann MH. Therapeutic and adverse actions of serotonin transporter substrates. Pharmacology and Therapeutics, 2002;95(1):73–88. https://doi.org/10.1016/S0163-7258(02)00234-6
18. McCann UD, Mertl M, Eligulashvili V and Ricaurte GA. Cognitive performance in (+/)3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) users: A controlled study. Psychopharmacology, 1999;143(4):417–425. https://doi.org/10.1007/s002130050967
19. Sprague JE, Everman SL and Nichols DE. An integrated hypothesis for the serotonergic axonal loss induced by 3, 4-methylenedioxymethamphetamine. Neurotoxicology, 1998;19(3):427-441.
20. Kyser TL, Hemmerle AM, Easley KE, Schmeltzer SN, Dickerson JW, Lundgren KH, Schaefer TL, Williams, MT, Vorhees CV and Seroogy KB. Acute effects of MDMA and methamphetamine on expression of GAD mRNA in adult rat forebrain. Program No. 472.09. Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2011. Online.
21. Collins SA, Huff C, Chiaia N, Gudelsky GA and Yamamoto BK. 3,4-methylenedioxymethamphetamine increases excitability in the dentate gyrus: Role of 5HT2A, 2016;136:1074-1084. https://doi.org/10.1111/jnc.13493
22. Nash JF and Yamamoto BK. Methamphetamine neurotoxicity and striatal glutamate release: comparison to 3,4-methylenedioxymethamphetamine. Brain research, 1992;581(2):237‐243.
23. Anneken JH and Gudelsky GA. MDMA produces a delayed and sustained increase in the extracellular concentration of glutamate in the rat hippocampus. Neuropharmacology 2012; 63:1022–1027.
24. Thiriet N, Ladenheim B, McCOY MT and Cadet JL. Analysis of ecstasy (MDMA)-induced transcriptional responses in the rat cortex. The FASEB journal, 2002;16(14):1887-1894.
25. Paris JM and Cunningham KA. Lack of serotonin neurotoxicity after intraraphe microinjection of (+)-3,4-methylenedioxymethamphetamine (MDMA). Brain Research Bulletin, 1992;28(1):115-119.
26. Colado MI and Richard A. The spin trap reagent α-phenyl-N-tert-butylnitrone prevents ‘ecstasy’-induced neurodegeneration of 5-hydroxytryptamine neurones. European Journal of Pharmacology, 1995;280(3):343-346.
27. Amato JL, Bankson, MG and Yamamoto BK. Prior exposure to chronic stress and MDMA potentiates mesoaccumbens dopamine release mediated by the 5-HT1B receptor. Neuropsychopharmacology, 2007; 32(4): 946.
28. Parrott AC. MDMA, serotonergic neurotoxicity, and the diverse functional deficits of recreational “Ecstasy” users. Neuroscience and Biobehavioral Reviews, 2013;37(8):1466–1484. https://doi.org/10.1016/j.neubiorev.2013.04.016
29. Brinker T, Stopa E, Morrison J and Klinge P. A new look at cerebrospinal fluid circulation. Fluids and Barriers of the CNS, 2014;11(1):10. https://doi.org/10.1186/2045-8118-11- 10
30. Pardridge WM. Drug transport in brain via the cerebrospinal fluid. Fluids and Barriers of the CNS, 2011;8(1):7. https://doi.org/10.1186/2045-8118-8-7
31. Sharma A, Sane H, Nagrajan A, Gokulchandran N, Badhe P, Paranjape A and Biju H. Autologous bone marrow mononuclear cells in ischemic cerebrovascular accident paves way for neurorestoration: a case report. Case Reports in Medicine, 2014, 530239. https://doi.org/10.1155/2014/530239
32. Aluise CD, Sowell RA and Butterfield DA. Peptides and proteins in plasma and cerebrospinal fluid as biomarkers for the prediction, diagnosis and monitoring of therapeutic efficacy of Alzheimer's disease. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 2008; 1782(10): 549-558.
33. Jones HC. Cerebrospinal Fluid Research: A new platform for dissemination of research, opinions and reviews with a common theme. Cerebrospinal fluid research, 2004,1(1):1.
34. Atulya M, Angel A and Mathew JA. A non-invasive method of cerebrospinal fluid collection from rats for assessing the cerebrospinal fluid drug content. Research Journal of Pharmacy and Technology, 2021;14(8)
35. O’Callaghan JP and Sriram K. Glial fibrillary acidic protein and related glial proteins as biomarkers of neurotoxicity. Expert Opinion on Drug Safety, 2005;4(3):433-442.
36. Petzold A, Stiefel D and Copp AJ. Amniotic fluid brain‐specific proteins are biomarkers for spinal cord injury in experimental myelomeningocele. Journal of Neurochemistry, 2005;95(2):594-598: 4085-4086.doi:10.52711/0974-360X.2021.00707.
37. Glushakova OY, Jeromin A, Martinez J, Johnson D, Denslow N, Streeter, J, … Mondello S.. Cerebrospinal fluid protein biomarker panel for assessment of neurotoxicity induced by kainic acid in rats. Toxicological Sciences, 2012;130(1):158–167. https://doi.org/10.1093/toxsci/kfs224
38. Tarnaris A, Watkins LD and Kitchen ND. Biomarkers in chronic adult hydrocephalus. Cerebrospinal Fluid Research, 2006;3(11). https://doi.org/10.1186/1743-8454-3-11
39. Lardinois O, Kirby PJ, Morgan DL, Sills RC, Tomer KB and Deterding LJ. Mass spectrometric analysis of rat cerebrospinal fluid proteins following exposure to the neurotoxicant carbonyl sulfide. Rapid Communications in Mass Spectrometry, 2014;28(23):2531-2538.
40. Lunardi G, Galati S, Tropepi D, Moschella V, Brusa L, Pierantozzi M, … Pisani A. Correlation between changes in CSF dopamine turnover and development of dyskinesia in Parkinson’s disease. Parkinsonism and Related Disorders, 2009;15(5), 383–389. https://doi.org/10.1016/j.parkreldis.2008.10.001
41. Bates CA and Zheng W. Brain disposition of α-Synuclein: roles of brain barrier systems and implications for Parkinson’s disease. Fluids and Barriers of the CNS, 2014; 11(1):17.
42. Kochanek PM, Berger RP, Bayir H, Wagner AK, Jenkins LW and Clark RS. Biomarkers of primary and evolving damage in traumatic and ischemic brain injury: Diagnosis, prognosis, probing mechanisms and therapeutic decision making. Curr. Opin. Crit. Care 2008;14:135–141.
43. Abbas AC, Al-Kraity WRH and Abbas EC. Effect antioxidant and serotonin level in the sera on Type II Diabetes Mellitus males patients and compare with control group. Research Journal of Pharmacy and Technology 2019; 12:5: 2453-2460. doi: 10.5958/0974-360X.2019.00411.6
44. Saulin AI, Savli M and Lanzenberger R. Serotonin and molecular neuroimaging in humans using PET. Amino Acids 2012;42:2039–2057. doi: 10.1007/s00726-011-1078-9
45. McCorvy JD and Roth BL. Structure and function of serotonin G protein-coupled receptors. Pharmacol. Ther. 2015; 150:129–142. doi: 10.1016/j. Pharmthera.2015.01.009
46. Borroto-Escuela DO, Agnati LF, Bechter K, Jansson A, Tarakanov AO and Fuxe K. The role of transmitter diffusion and flow versus extracellular vesicles in volume transmission in the brain neural–glial networks. Phil. Trans. R. Soc. B, 2015;370(20):140-183.
47. Buhot MC, Wolff M, Benhassine N, Costet P, Hen R, Segu L. Spatial learning in the 5-HT1B receptor knockout mouse: selective facilitation/impairment depending on the cognitive demand. Learn Mem 2003; 10:466–477.
48. Rodríguez JJ, Noristani HN and Verkhratsky A. The serotonergic system in ageing and Alzheimer’s disease. Progress in Neurobiology, 2012;99(1):15–41. https://doi.org/10.1016/j.pneurobio.2012.06.010
49. Barlow RL, Alsiö J, Jupp B, Rabinovich R, Shrestha S, Roberts AC, … Dalley JW. Markers of serotonergic function in the orbitofrontal cortex and dorsal raphé nucleus predict individual variation in spatial-discrimination serial reversal learning. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 2015; 40(7):1619–30. https://doi.org/10.1038/npp.2014.335
50. Kema IP, de Vries EG, Muskiet FA. Clinical chemistry of serotonin and metabolites. J Chromatogr B Biomed Sci Appl. 2000 Sep 29;747(1-2):33-48. doi: 10.1016/s0378-4347(00)00341-8. PMID: 11103898.
51. (MDMA or “Ecstasy”). Psychopharmacology, 1995;119(3):247-260.
52. Rudnick G and 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, 1992;89(5):1817-1821.
53. Green AR, Cross AJ and Goodwin GM. Review of the pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA or “Ecstasy”). Psychopharmacology, 1995;119(3):247-260.
54. Gillman P. A review of serotonin toxicity data: implications for the mechanisms of antidepressant drug action. Biol Psychiatry, 2006; 59:1046-1051.
55. Huff C, Bhide N, Schroering A, Yamamoto B K and Gudelsky GA. Effect of repeated exposure to MDMA on the function of the 5-HT transporter as assessed by synaptosomal 5-HT uptake. Brain research bulletin, 2013;91:52-57.
56. Barrionuevo M, Aguirre N, Del Río J and Lasheras B. Serotonergic deficits and impaired passive-avoidance learning in rats by MDEA: A comparison with MDMA. Pharmacology Biochemistry and Behavior, 2000; 65(2): 233–240. https://doi.org/10.1016/S0091-3057(99)00170-7
57. Bruno A, Nolte KB and Chapin J. Stroke associated with ephedrine use. Neurology, 1993;43(7):1313-1313.
58. Nicholls DG. Mitochondrial dysfunction and glutamate excitotoxicity studied in primary neuronal cultures. Current Molecular Medicine, 2004;4(2):149-177.
59. Preedy VR (Ed.) 2016. Neuropathology of Drug Addictions and Substance Misuse Volume 3: General Processes and Mechanisms, Prescription Medications, Caffeine and Areca, Polydrug Misuse, Emerging Addictions and Non-Drug Addictions. Academic Press.
60. Halpin LE, Collins SA and Yamamoto BK. Neurotoxicity of methamphetamine and 3,4-methylenedioxymethamphetamine. Life Sciences, 2014;97(1):37–44. https://doi.org/10.1016/j.lfs.2013.07.014
61. Sanzgiri RP, Araque A and Haydon PG. Prostaglandin E2 stimulates glutamate receptor-dependent astrocyte neuromodulation in cultured hippocampal cells. Journal of Neurobiology, 1999;41(2):221-229.
62. Ahmad AS, Zhuang H, Echeverria V, and Doré S. Stimulation of prostaglandin EP2 receptors prevents NMDA-induced excitotoxicity. Journal of neurotrauma, 2006; 23(12): 1895-1903.
63. Mohan S and Glushakov AV. Contribution of PGE2 EP1 receptor in hemin- induced neurotoxicity. Frontiers in molecular neuroscience, 2013; https://doi.org/10.3389/fnmol.2013.00031.
64. Ayfan AH, Muslim RF, Saleh MM. Preparation, Diagnoses of Novel hetero atom compounds and Evaluation the Antibacterial Activity of them. Research J. Pharm. and Tech. 2021; 14(1):79-84. doi: 10.5958/0974-360X.2021.00015.9
65. Bilal M, Al-Saleh J, Fakher FA. Serum levels of prostaglandin E2 (PGE2) and interleukin 17 (IL-17) are associated with Angiogenesis and Metastasis in breast cancer patients. Research J. Pharm. and Tech. 2021; 14(1):317-320. doi: 10.5958/0974-360X.2021.00058.5
66. Ayoub BM. Pleiotropic Repositioning of Metformin as a Potential Pluripotent Drug. Research J. Pharm. and Tech. 2019; 12(12): 5716-5722. doi: 10.5958/0974-360X.2019.00989.2
67. Khirfan R, Bhagat V, Tengku MA, Awang Z, Khlaifa M, AlRammah T, AlAzmi A. The study on the influential factors on cost containment in health care. Research J. Pharm. and Tech. 2019; 12(11): 5157-5162. doi: 10.5958/0974-360X.2019.00892.8
68. Choubey A, Kumar H, Jain S. A Systematic Review on Neurobehaviour and Neuroendocrine disorders. Research J. Pharm. and Tech. 2020; 13(11):5510-5514. doi: 10.5958/0974-360X.2020.00962.2
69. Mahajan N, Shende S, Dumore N, Nasare L. Development and Evaluation of Ion Induced in Situ Gelling System of Opoid Analgesic for Nose to Brain Delivery. Research J. Pharm. and Tech. 2019; 12(10):4741-4746. doi: 10.5958/0974-360X.2019.00817.5
70. Rajendran G, Jayalalitha S, Adalarasu K, Nirmalraj T. Development of single channel EEG Acquisition system for BCI applications. Research Journal of Pharmacy and Technology. 2021; 14(9):4705-9. doi: 10.52711/0974-360X.2021.00818
71. Ahamed S, Sumitra M, Chitra V. Prevalance and role of Melatonin on PCOS in its treatment using Herbal Drugs. Research Journal of Pharmacy and Technology. 2021; 14(9):5029-3. doi: 10.52711/0974-360X.2021.00877