Mutations in monoamine oxidase (MAO) genes in mice lead to hypersensitivity to serotonin-enhancing drugs: Implications for drug side effects in humans

Pharmacogenomics Journal

Volumn 13, Issue 6, 2013, Pages 551-557

  Fox, M A ^a   Panessiti, M G ^a   Moya, P R ^a   Tolliver, T J ^a   Chen, K ^b   Shih, J C ^b,c   Murphy, D L ^a  

^a NATIONAL INSTITUTE OF MENTAL HEALTH   (United States)

^b UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^c UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

5 hydroxy L tryptophan (5 HTP); monoamine oxidase (MAO) A B knockout mice; serotonin syndrome; tramadol

Indexed keywords

5 HYDROXYTRYPTOPHAN; AMINE OXIDASE (FLAVIN CONTAINING) ISOENZYME A; AMINE OXIDASE (FLAVIN CONTAINING) ISOENZYME B; SEROTONIN; SEROTONIN TRANSPORTER; TRAMADOL;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; DRUG HYPERSENSITIVITY; FEMALE; GENE; GENE EXPRESSION; GENE MUTATION; GENETIC MODEL; GENETIC POLYMORPHISM; GENETIC SUSCEPTIBILITY; HUMAN; KNOCKOUT MOUSE; MAOA GENE; MAOB GENE; MOUSE; NONHUMAN; PRIORITY JOURNAL; SEROTONIN SYNDROME; SEROTONINERGIC SYSTEM; TISSUE LEVEL; WILD TYPE;

MUS;

ANIMALS; BASE SEQUENCE; DNA PRIMERS; DRUG HYPERSENSITIVITY; MICE; MICE, KNOCKOUT; MONOAMINE OXIDASE; MUTATION; SEROTONIN UPTAKE INHIBITORS;

EID: 84888134595     PISSN: 1470269X     EISSN: 14731150     Source Type: Journal    
DOI: 10.1038/tpj.2012.35     Document Type: Article

References (73)

1. Isbister GK, Buckley NA. The pathophysiology of serotonin toxicity in animals and humans: implications for diagnosis and treatment. Clin Neuropharmacol 2005; 28: 205-214.
2. Pilgrim JL, Gerostamoulos D, Drummer OH. Deaths involving contraindicated and inappropriate combinations of serotonergic drugs. Int J Legal Med 2011; 125: 803-815.
3. Gnanadesigan N, Espinoza RT, Smith R, Israel M, Reuben DB. Interaction of serotonergic antidepressants and opioid analgesics: Is serotonin syndrome going undetected? J Am Med Dir Assoc, 2005; 6: 265-269.
4. Garrett PM. Tramadol overdose and serotonin syndrome manifesting as acute right heart dysfunction. Anaesth Intensive Care 2004; 32: 575-577.
5. Gillman PK. Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. Br J Anaesth 2005; 95: 434-441.
6. Mason BJ, Blackburn KH. Possible serotonin syndrome associated with tramadol and sertraline coadministration. Ann Pharmacother 1997; 31: 175-177.
7. Houlihan DJ. Serotonin syndrome resulting from coadministration of tramadol, venlafaxine, and mirtazapine. Ann Pharmacother 2004; 38: 411-413.
8. Vizcaychipi MP, Walker S, Palazzo M. Serotonin syndrome triggered by tramadol. Br J Anaesth 2007; 99: 919.
9. Kesavan S, Sobala GM. Serotonin syndrome with fluoxetine plus tramadol. J R Soc Med 1999; 92: 474-475.
10. Mittino D, Mula M, Monaco F. Serotonin syndrome associated with tramadolsertraline coadministration. Clin Neuropharmacol 2004; 27: 150-151.
11. Lantz MS, Buchalter EN, Giambanco V. Serotonin syndrome following the administration of tramadol with paroxetine. Int J Geriatr Psychiatry 1998; 13: 343-345.
12. Peacock LE, Wright F. Serotonin syndrome secondary to tramadol and citalopram. Age Ageing 40: 528.
13. Dayer P, Collart L, Desmeules J. The pharmacology of tramadol. Drugs 1994; 47(Suppl 1): 3-7.
14. Hennies HH, Friderichs E, Wilsmann K, Flohe L. Effect of the opioid analgesic tramadol on inactivation of norepinephrine and serotonin. Biochem Pharmacol 1982; 31: 1654-1655.
15. Raffa RB, Friderichs E, Reimann W, Shank RP, Codd EE, Vaught JL. Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an 'atypical' opioid analgesic. J Pharmacol Exp Ther 1992; 260: 275-285.
16. Munro G, Baek CA, Erichsen HK, Nielsen AN, Nielsen EO, Scheel-Kruger J et al. The novel compound (/-)-1-[10-((E)-3-Phenyl-allyl)-3,10-diaza-bicyclo[4. 3. 1]dec-3-yl]-propan-1-one (NS7051) attenuates nociceptive transmission in animal models of experimental pain; a pharmacological comparison with the combined muopioid receptor agonist and monoamine reuptake inhibitor tramadol. Neuropharmacology 2008; 54: 331-343.
17. Bloms-Funke P, Dremencov E, Cremers TI, Tzschentke TM. Tramadol increases extracellular levels of serotonin and noradrenaline as measured by in vivo microdialysis in the ventral hippocampus of freely-moving rats. Neurosci Lett 2011; 490: 191-195.
18. Fox MA, Jensen CL, French HT, Stein AR, Huang SJ, Tolliver TJ et al. Neurochemical, behavioral, and physiological effects of pharmacologically enhanced serotonin levels in serotonin transporter (SERT)-deficient mice. Psychopharmacology (Berl) 2008; 201: 203-218.
19. Fox MA, Jensen CL, Gallagher PS, Murphy DL. Receptor mediation of exaggerated responses to serotonin-enhancing drugs in serotonin transporter (SERT)-deficient mice. Neuropharmacology 2007; 53: 643-656.
20. Izumi T, Iwamoto N, Kitaichi Y, Kato A, Inoue T, Koyama T. Effects of co-administration of a selective serotonin reuptake inhibitor and monoamine oxidase inhibitors on 5-HT-related behavior in rats. Eur J Pharmacol 2006; 532: 258-264.
21. Sternbach H. The serotonin syndrome. Am J Psychiatry 1991; 148: 705-713.
22. Bortolato M, Chen K, Shih JC. Monoamine oxidase inactivation: from pathophysiology to therapeutics. Adv Drug Deliv Rev 2008; 60: 1527-1533.
23. Shih JC. Molecular basis of human MAO A and B. Neuropsychopharmacology 1991; 4: 1-7.
24. Shih JC, Chen K, Ridd MJ. Monoamine oxidase: from genes to behavior. Annu Rev Neurosci 1999; 22: 197-217.
25. Cases O, Seif I, Grimsby J, Gaspar P, Chen K, Pournin S et al. Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA. Science 1995; 268: 1763-1766.
26. Evrard A, Malagie I, Laporte AM, Boni C, Hanoun N, Trillat AC et al. Altered regulation of the 5-HT system in the brain of MAO-A knock-out mice. Eur J Neurosci 2002; 15: 841-851.
27. Owesson CA, Hopwood SE, Callado LF, Seif I, McLaughlin DP, Stamford JA. Altered presynaptic function in monoaminergic neurons of monoamine oxidase-A knockout mice. Eur J Neurosci 2002; 15: 1516-1522.
28. Holschneider DP, Chen K, Seif I, Shih JC. Biochemical, behavioral, physiologic, and neurodevelopmental changes in mice deficient in monoamine oxidase A or B. Brain Res Bull 2001; 56: 453-462.
29. Grimsby J, Toth M, Chen K, Kumazawa T, Klaidman L, Adams JD et al. Increased stress response and beta-phenylethylamine in MAOB-deficient mice. Nat Genet 1997; 17: 206-210.
30. Chen K, Holschneider DP, Wu W, Rebrin I, Shih JC. A spontaneous point mutation produces monoamine oxidase A/B knock-out mice with greatly elevated monoamines and anxiety-like behavior. J Biol Chem 2004; 279: 39645-39652.
31. Murphy DL, Fox MA, Timpano KR, Moya PR, Ren-Patterson R, Andrews AM et al. How the serotonin story is being rewritten by new gene-based discoveries principally related to SLC6A4, the serotonin transporter gene, which functions to influence all cellular serotonin systems. Neuropharmacology 2008; 55: 932-960.
32. Fox MA, Andrews AM, Wendland JR, Lesch KP, Holmes A, Murphy DL. A pharmacological analysis of mice with a targeted disruption of the serotonin transporter. Psychopharmacology (Berl) 2007; 195: 147-166.
33. Fox MA, Jensen CL, Murphy DL. Tramadol and another atypical opioid meperidine have exaggerated serotonin syndrome behavioural effects, but decreased analgesic effects, in genetically deficient serotonin transporter (SERT) mice. Int J Neuropsychopharmacol 2009; 12: 1055-1065.
34. Kalueff AV, Fox MA, Gallagher PS, Murphy DL. Hypolocomotion anxiety and serotonin syndrome-like behavior contribute to the complex phenotype of serotonin transporter knockout mice. Genes Brain Behav 2007; 6: 389-400.
35. Diaz SL, Maroteaux L. Implication of 5-HT(2B) receptors in the serotonin syndrome. Neuropharmacology 2011; 61: 495-502.
36. Jacobs BL. An animal behavior model for studying central serotonergic synapses. Life Sci 1976; 19: 777-785.
37. Bengel D, Murphy DL, Andrews AM, Wichems CH, Feltner D, Heils A et al. Altered brain serotonin homeostasis and locomotor insensitivity to 3, 4-methylenedioxymethamphetamine ("Ecstasy") in serotonin transporter-deficient mice. Mol Pharmacol 1998; 53: 649-655.
38. Kim DK, Tolliver TJ, Huang SJ, Martin BJ, Andrews AM, Wichems C et al. Altered serotonin synthesis, turnover and dynamic regulation in multiple brain regions of mice lacking the serotonin transporter. Neuropharmacology 2005; 49: 798-810.
39. Cases O, Lebrand C, Giros B, Vitalis T, De Maeyer E, Caron MG et al. Plasma membrane transporters of serotonin, dopamine, and norepinephrine mediate serotonin accumulation in atypical locations in the developing brain of monoamine oxidase A knock-outs. J Neurosci 1998; 18: 6914-6927.
40. Holschneider DP, Scremin OU, Huynh L, Chen K, Seif I, Shih JC. Regional cerebral cortical activation in monoamine oxidase A-deficient mice: differential effects of chronic versus acute elevations in serotonin and norepinephrine. Neuroscience 2000; 101: 869-877.
41. Zhou FC, Lesch KP, Murphy DL. Serotonin uptake into dopamine neurons via dopamine transporters: a compensatory alternative. Brain Res 2002; 942: 109-119.
42. Mathews TA, Fedele DE, Coppelli FM, Avila AM, Murphy DL, Andrews AM. Gene dose-dependent alterations in extraneuronal serotonin but not dopamine in mice with reduced serotonin transporter expression. J Neurosci Methods 2004; 140: 169-181.
43. Zhang G, Krishnamoorthy S, Ma Z, Vukovich NP, Huang X, Tao R. Assessment of 5-hydroxytryptamine efflux in rat brain during a mild, moderate and severe serotonin-toxicity syndrome. Eur J Pharmacol 2009; 615: 66-75.
44. D'Souza UM, Craig IW. Functional genetic polymorphisms in serotonin and dopamine gene systems and their significance in behavioural disorders. Prog Brain Res 2008; 172: 73-98.
45. O'Leary RE, Shih JC, Hyland K, Kramer N, Asher YJ, Graham Jr JM. De novo microdeletion of Xp11. 3 exclusively encompassing the monoamine oxidase A and B genes in a male infant with episodic hypotonia: A genomics approach to personalized medicine. Eur J Med Genet 2012; 55: 349-353.
46. Whibley A, Urquhart J, Dore J,Willatt L, Parkin G, Gaunt L et al. Deletion of MAOA and MAOB in a male patient causes severe developmental delay, intermittent hypotonia and stereotypical hand movements. Eur J Hum Genet 2010; 18: 1095-1099.
47. Collins FA, Murphy DL, Reiss AL, Sims KB, Lewis JG, Freund L et al. Clinical, biochemical, and neuropsychiatric evaluation of a patient with a contiguous gene syndrome due to a microdeletion Xp11. 3 including the Norrie disease locus and monoamine oxidase (MAOA and MAOB) genes. Am J Med Genet 1992; 42: 127-134.
48. Murphy DL, Sims K, Eisenhofer G, Greenberg BD, George T, Berlin F et al. Are MAO-A deficiency states in the general population and in putative high-risk populations highly uncommon? J Neural Transm Suppl 1998; 52: 29-38.
49. Deckert J, Catalano M, Syagailo YV, Bosi M, Okladnova O, Di Bella D et al. Excess of high activity monoamine oxidase A gene promoter alleles in female patients with panic disorder. Hum Mol Genet 1999; 8: 621-624.
50. Sabol SZ, Hu S, Hamer D. A functional polymorphism in the monoamine oxidase A gene promoter. Hum Genet 1998; 103: 273-279.
51. Balciuniene J, Emilsson L, Oreland L, Pettersson U, Jazin E. Investigation of the functional effect of monoamine oxidase polymorphisms in human brain. Hum Genet 2002; 110: 1-7.
52. Lenders JW, Eisenhofer G, Abeling NG, Berger W, Murphy DL, Konings CH et al. Specific genetic deficiencies of the A and B isoenzymes of monoamine oxidase are characterized by distinct neurochemical and clinical phenotypes. J Clin Invest 1996; 97: 1010-1019.
53. Brunner HG, Nelen M, Breakefield XO, Ropers HH, van Oost BA. Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A. Science 1993; 262: 578-580.
54. Kim-Cohen J, Caspi A, Taylor A, Williams B, Newcombe R, Craig IW et al. MAOA, maltreatment, and gene-environment interaction predicting children's mental health: new evidence and a meta-analysis. Mol Psychiatry 2006; 11: 903-913.
55. Samochowiec J, Lesch KP, Rottmann M, Smolka M, Syagailo YV, Okladnova O et al. Association of a regulatory polymorphism in the promoter region of the monoamine oxidase A gene with antisocial alcoholism. Psychiatry Res 1999; 86: 67-72.
56. Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW et al. Role of genotype in the cycle of violence in maltreated children. Science 2002; 297: 851-854.
57. Contini V, Marques FZ, Garcia CE, Hutz MH, Bau CH. MAOA-uVNTR polymorphism in a Brazilian sample: further support for the association with impulsive behaviors and alcohol dependence. Am J Med Genet B Neuropsychiatr Genet 2006; 141B: 305-308.
58. Meyer-Lindenberg A, Buckholtz JW, Kolachana B, Hariri AR, Pezawas L, Blasi G et al. Neural mechanisms of genetic risk for impulsivity and violence in humans. Proc Natl Acad Sci USA 2006; 103: 6269-6274.
59. Williams LM, Gatt JM, Kuan SA, Dobson-Stone C, Palmer DM, Paul RH et al. A polymorphism of the MAOA gene is associated with emotional brain markers and personality traits on an antisocial index. Neuropsychopharmacology 2009; 34: 1797-1809.
60. Cohen IL, Liu X, Schutz C, White BN, Jenkins EC, Brown WT et al. Association of autism severity with a monoamine oxidase A functional polymorphism. Clin Genet 2003; 64: 190-197.
61. Yoo HJ, Lee SK, Park M, Cho IH, Hyun SH, Lee JC et al. Family-and populationbased association studies of monoamine oxidase A and autism spectrum disorders in Korean. Neurosci Res 2009; 63: 172-176.
62. Aklillu E, Karlsson S, Zachrisson OO, Ozdemir V, Agren H. Association of MAOA gene functional promoter polymorphism with CSF dopamine turnover and atypical depression. Pharmacogenet Genomics 2009; 19: 267-275.
63. Yu YW, Tsai SJ, Hong CJ, Chen TJ, Chen MC, Yang CW. Association study of a monoamine oxidase a gene promoter polymorphism with major depressive disorder and antidepressant response. Neuropsychopharmacology 2005; 30: 1719-1723.
64. Xie P, Kranzler HR, Poling J, Stein MB, Anton RF, Brady K et al. Interactive effect of stressful life events and the serotonin transporter 5-HTTLPR genotype on posttraumatic stress disorder diagnosis in 2 independent populations. Arch Gen Psychiatry 2009; 66: 1201-1209.
65. Dunkley EJ, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM 2003; 96: 635-642.
66. Bonetto N, Santelli L, Battistin L, Cagnin A. Serotonin syndrome and rhabdomyolysis induced by concomitant use of triptans, fluoxetine and hypericum. Cephalalgia 2007; 27: 1421-1423.
67. Ng BK, Cameron AJ. The role of methylene blue in serotonin syndrome: a systematic review. Psychosomatics 2010; 51: 194-200.
68. Packer S, Berman SA. Serotonin syndrome precipitated by the monoamine oxidase inhibitor linezolid. Am J Psychiatry 2007; 164: 346-347.
69. Kuehn B. Serotonin Syndrome Update. J Am Med Assoc 2011; 306: 2261.
70. Ringland C, Mant A, McGettigan P, Mitchell P, Kelman C, Buckley N et al. Uncovering the potential risk of serotonin toxicity in Australian veterans using pharmaceutical claims data. Br J Clin Pharmacol 2008; 66: 682-688.
71. Hu XZ, Lipsky RH, Zhu G, Akhtar LA, Taubman J, Greenberg BD et al. Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. Am J Hum Genet 2006; 78: 815-826.
72. Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 1996; 274: 1527-1531.
73. Praschak-Rieder N, Kennedy J, Wilson AA, Hussey D, Boovariwala A, Willeit M et al. Novel 5-HTTLPR allele associates with higher serotonin transporter binding in putamen: a [(11)C] DASB positron emission tomography study. Biol Psychiatry 2007; 62: 327-331.