Tramadol and another atypical opioid meperidine have exaggerated serotonin syndrome behavioural effects, but decreased analgesic effects, in genetically deficient serotonin transporter (SERT) mice

International Journal of Neuropsychopharmacology

Volumn 12, Issue 8, 2009, Pages 1055-1065

  Fox, Meredith A ^a   Jensen, Catherine L ^a   Murphy, Dennis L ^a  

^a NATIONAL INSTITUTE OF MENTAL HEALTH   (United States)

Author keywords

Hot plate analgesia; Meperidine; Morphine; Serotonin syndrome; Serotonin transporter knockout mice; Tramadol

Indexed keywords

5 HYDROXYTRYPTOPHAN; ANTIDEPRESSANT AGENT; MONOAMINE OXIDASE INHIBITOR; MORPHINE; N [2 [4 (2 METHOXYPHENYL) 1 PIPERAZINYL]ETHYL] N (2 PYRIDYL)CYCLOHEXANECARBOXAMIDE; PETHIDINE; SEROTONIN TRANSPORTER; TRAMADOL; TRANYLCYPROMINE;

ANALGESIA; ANALGESIC ACTIVITY; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BEHAVIOR; CONTROLLED STUDY; DRUG INDUCED DISEASE; EXPERIMENTAL MODEL; EXPERIMENTAL MOUSE; FEMALE; GENETIC MODEL; HETEROZYGOTE; KNOCKOUT MOUSE; MOUSE; NONHUMAN; PRIORITY JOURNAL; RODENT; SEROTONIN SYNDROME; WILD TYPE;

ANALGESICS, OPIOID; ANALYSIS OF VARIANCE; ANIMALS; BEHAVIOR, ANIMAL; BEHAVIORAL SYMPTOMS; DISEASE MODELS, ANIMAL; DRUG INTERACTIONS; DRUG SYNERGISM; FEMALE; MEPERIDINE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; PAIN MEASUREMENT; PIPERAZINES; PYRIDINES; SEROTONIN ANTAGONISTS; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; TRAMADOL;

EID: 69749114328     PISSN: 14611457     EISSN: 14695111     Source Type: Journal    
DOI: 10.1017/S146114570900011X     Document Type: Article

References (85)

1. Aceto MD, McKean DB, Pearl J (1969). Effects of opiates and opiate antagonists on the Straub tail reaction in mice. British Journal of Pharmacology 36, 225-239.
2. Altman EM, Manos GH (2007). Serotonin syndrome associated with citalopram and meperidine. Psychosomatics 48, 361-363.
3. Bamigbade TA, Davidson C, Langford RM, Stamford JA (1997). Actions of tramadol, its enantiomers and principal metabolite, O-desmethyltramadol, on serotonin (5-HT) efflux and uptake in the rat dorsal raphe nucleus. British Journal of Anaesthesia 79, 352-356.
4. Basselin M, Fox MA, Chang L, Bell JM, Greenstein D, Chen M, Murphy DL, Rapoport SI (2009). Imaging elevated brain arachidonic acid signaling in unanesthetized serotonin transporter (5-HTT)-deficient mice. Published online: 14 January 2009. Neuropsychopharmacology 2009. doi:10.1038/npp.2008.227.
5. Belknap JK, Noordewier B, Lame M (1989). Genetic dissociation of multiple morphine effects among C57BL/ 6J, DBA/2J and C3H/HeJ inbred mouse strains. Physiology and Behavior 46, 69-74.
6. Bengel D, Murphy DL, Andrews AM, Wichems CH, Feltner D, Heils A, Mossner R, Westphal H, Lesch KP (1998). Altered brain serotonin homeostasis and locomotor insensitivity to 3,4-methylenedioxymethamphetamine ('Ecstasy') in serotonin transporter-deficient mice. Molecular Pharmacology 53, 649-655.
7. Berrocoso E, De Benito MD, Mico JA (2007). Role of serotonin 5-HT1A and opioid receptors in the antiallodynic effect of tramadol in the chronic constriction injury model of neuropathic pain in rats. Psychopharmacology 193, 97-105.
8. Berrocoso E, Rojas-Corrales MO, Mico JA (2006). Differential role of 5-HT1A and 5-HT1B receptors on the antinociceptive and antidepressant effect of tramadol in mice. Psychopharmacology 188, 111-118.
9. Bonetto N, Santelli L, Battistin L, Cagnin A (2007). Serotonin syndrome and rhabdomyolysis induced by concomitant use of triptans, fluoxetine and hypericum. Cephalalgia 27, 1421-1423.
10. Bouali S, Evrard A, Chastanet M, Lesch KP, Hamon M, Adrien J (2003). Sex hormone-dependent desensitization of 5-HT1A autoreceptors in knockout mice deficient in the 5-HT transporter. European Journal of Neuroscience 18, 2203-2212.
11. Choong K, Ghiculescu RA (2008). Iatrogenic neuropsychiatric syndromes. Australian Family Physician 37, 627-629.
12. Dannawi M (2002). Possible serotonin syndrome after combination of buspirone and St John's Wort. Journal of Psychopharmacology 16, 401.
13. Das PK, Warkentin DI, Hewko R, Forrest DL (2008). Serotonin syndrome after concomitant treatment with linezolid and meperidine. Clinical Infectious Diseases 46, 264-265.
14. Dayer P, Collart L, Desmeules J (1994). The pharmacology of tramadol. Drugs 47 (Suppl. 1), 3-7.
15. Desmeules JA, Piguet V, Collart L, Dayer P (1996). Contribution of monoaminergic modulation to the analgesic effect of tramadol. British Journal of Clinical Pharmacology 41, 7-12.
16. Dougherty JA, Young H, Shafi T (2002). Serotonin syndrome induced by amitriptyline, meperidine, and venlafaxine. Annals of Pharmacotherapy 36, 1647-1648.
17. Driessen B, Reimann W (1992). Interaction of the central analgesic, tramadol, with the uptake and release of 5-hydroxytryptamine in the rat brain in vitro. British Journal of Pharmacology 105, 147-151.
18. Dunkley EJ, Isbister GK, Sibbritt D, Dawson AH, Whyte IM (2003). The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. Quarterly Journal of Medicine 96, 635-642.
19. Dursun SM, Handley SL (1996). Similarities in the pharmacology of spontaneous and DOI-induced head-shakes suggest 5HT2A receptors are active under physiological conditions. Psychopharmacology 128, 198-205.
20. Fanelli J, Montgomery C (1998). Use of the analgesic tramadol in antidepressant potentiation. Psychopharmacology Bulletin 32, 442.
21. Fox M, Jensen C, Gallagher P, Murphy DL (2007). Receptor mediation of exaggerated responses to serotonin-enhancing drugs in serotonin transporter (SERT)-deficient mice. Neuropharmacology 53, 643-656.
22. Fox MA, Jensen CL, French HT, Stein AR, Huang SJ, Tolliver TJ, Murphy DL (2008). Neurochemical, behavioral, and physiological effects of pharmacologically enhanced serotonin levels in serotonin transporter (SERT)-deficient mice. Psychopharmacology 201, 203-218.
23. Garrett PM (2004). Tramadol overdose and serotonin syndrome manifesting as acute right heart dysfunction. Anaesthesia and Intensive Care 32, 575-577.
24. Gaynor CM, Handley SL (2001). Effects of nicotine on head-shakes and tryptophan metabolites. Psychopharmacology 153, 327-333.
25. Gillman PK (2005). Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. British Journal of Anaesthesia 95, 434-441.
26. Gillman PK (2006). A review of serotonin toxicity data: implications for the mechanisms of antidepressant drug action. Biological Psychiatry 59, 1046-1051.
27. Gnanadesigan N, Espinoza RT, Smith R, Israel M, Reuben DB (2005). Interaction of serotonergic antidepressants and opioid analgesics: Is serotonin syndrome going undetected? Journal of the American Medical Directors Association 6, 265-269.
28. Goldsmith TB, Shapira NA, Keck Jr. P.E. (1999). Rapid remission of OCD with tramadol hydrochloride. American Journal of Psychiatry 156, 660-661.
29. Hayslett RL, Tizabi Y (2005). Effects of donepezil, nicotine and haloperidol on the central serotonergic system in mice: implications for Tourette's syndrome. Pharmacology, Biochemistry and Behavior 81, 879-886.
30. Hennies HH, Friderichs E, Wilsmann K, Flohe L (1982). Effect of the opioid analgesic tramadol on inactivation of norepinephrine and serotonin. Biochemical Pharmacology 31, 1654-1655.
31. Holmes A, Lit Q, Murphy DL, Gold E, Crawley JN (2003). Abnormal anxiety-related behavior in serotonin transporter null mutant mice: the influence of genetic background. Genes, Brain, and Behavior 2, 365-380.
32. Holmes A, Yang RJ, Murphy DL, Crawley JN (2002). Evaluation of antidepressant-related behavioral responses in mice lacking the serotonin transporter. Neuropsychopharmacology 27, 914-923.
33. Houlihan DJ (2004). Serotonin syndrome resulting from coadministration of tramadol, venlafaxine, and mirtazapine. Annals of Pharmacotherapy 38, 411-413.
34. Hoyer D, Schoeffter P, Waeber C, Palacios JM (1990). Serotonin 5-HT1D receptors. Annals of the New York Academy of Sciences 600, 168-181; discussion 181-162.
35. Hu XZ, Lipsky RH, Zhu G, Akhtar LA, Taubman J, Greenberg BD, Xu K, Arnold PD, Richter MA, Kennedy JL, Murphy DL, Goldman D (2006). Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. American Journal of Human Genetics 78, 815-826.
36. Ide S, Minami M, Ishihara K, Uhl GR, Sora I, Ikeda K (2006). Mu opioid receptor-dependent and independent components in effects of tramadol. Neuropharmacology 51, 651-658.
37. Isbister GK, Buckley NA (2005). The pathophysiology of serotonin toxicity in animals and humans: implications for diagnosis and treatment. Clinical Neuropharmacology 28, 205-214.
38. Izumi T, Iwamoto N, Kitaichi Y, Kato A, Inoue T, Koyama T (2006). Effects of co-administration of a selective serotonin reuptake inhibitor and monoamine oxidase inhibitors on 5-HT-related behavior in rats. European Journal of Pharmacology 532, 258-264.
39. Jacobs BL (1976). An animal behavior model for studying central serotonergic synapses. Life Sciences 19, 777-785.
40. Kalueff AV, Fox MA, Gallagher PS, Murphy DL (2007). Hypolocomotion, anxiety and serotonin syndrome-like behavior contribute to the complex phenotype of serotonin transporter knockout mice. Genes, Brain, and Behavior 6, 389-400.
41. x/x knock-out male mice. Pain 130, 235-248.
42. Kennett GA, Dickinson SL, Curzon G (1985). Central serotonergic responses and behavioural adaptation to repeated immobilisation: the effect of the corticosterone synthesis inhibitor metyrapone. European Journal of Pharmacology 119, 143-152.
43. Kesavan S, Sobala GM (1999). Serotonin syndrome with fluoxetine plus tramadol. Journal of the Royal Society of Medicine 92, 474-475.
44. Lantz MS, Buchalter EN, Giambanco V (1998). Serotonin syndrome following the administration of tramadol with paroxetine. International Journal of Geriatric Psychiatry 13, 343-345.
45. Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S, Benjamin J, Muller CR, Hamer DH, Murphy DL (1996). Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274, 1527-1531.
46. Li Q, Wichems C, Heils A, Lesch KP, Murphy DL (2000). Reduction in the density and expression, but not G-protein coupling, of serotonin receptors (5-HT1A) in 5-HT transporter knock-out mice: gender and brain region differences. Journal of Neuroscience 20, 7888-7895.
47. Li Q, Wichems C, Heils A, Van De Kar LD, Lesch KP, Murphy DL (1999). Reduction of 5-hydroxytryptamine (5-HT)(1A)-mediated temperature and neuroendocrine responses and 5-HT(1A) binding sites in 5-HT transporter knockout mice. Journal of Pharmacology and Experimental Therapeutics 291, 999-1007.
48. Li Q, Wichems CH, Ma L, Van de Kar LD, Garcia F, Murphy DL (2003). Brain region-specific alterations of 5-HT2A and 5-HT2C receptors in serotonin transporter knockout mice. Journal of Neurochemistry 84, 1256-1265.
49. Lucki I, Nobler MS, Frazer A (1984). Differential actions of serotonin antagonists on two behavioral models of serotonin receptor activation in the rat. Journal of Pharmacology and Experimental Therapeutics 228, 133-139.
50. Mason BJ, Blackburn KH (1997). Possible serotonin syndrome associated with tramadol and sertraline coadministration. Annals of Pharmacotherapy 31, 175-177.
51. Millan MJ, Newman-Tancredi A, Audinot V, Cussac D, Lejeune F, Nicolas JP, Coge F, Galizzi JP, Boutin JA, Rivet JM, Dekeyne A, Gobert A (2000). Agonist and antagonist actions of yohimbine as compared to fluparoxan at alpha(2)-adrenergic receptors (AR)s, serotonin (5-HT)(1A), 5-HT(1B), 5-HT(1D) and dopamine D(2) and D(3) receptors. Significance for the modulation of frontocortical monoaminergic transmission and depressive states. Synapse 35, 79-95.
52. Mittino D, Mula M, Monaco F (2004). Serotonin syndrome associated with tramadol-sertraline coadministration. Clinical Neuropharmacology 27, 150-151.
53. Montanez S, Owens WA, Gould GG, Murphy DL, Daws LC (2003). Exaggerated effect of fluvoxamine in heterozygote serotonin transporter knockout mice. Journal of Neurochemistry 86, 210-219.
54. Oliva P, Aurilio C, Massimo F, Grella A, Maione S, Grella E, Scafuro M, Rossi F, Berrino L (2002). The antinociceptive effect of tramadol in the formalin test is mediated by the serotonergic component. European Journal of Pharmacology 445, 179-185.
55. Ozdogan UK, Lahdesmaki J, Scheinin M (2006). The analgesic efficacy of partial opioid agonists is increased in mice with targeted inactivation of the alpha2A-adrenoceptor gene. European Journal of Pharmacology 529, 105-113.
56. Packer S, Berman SA (2007). Serotonin syndrome precipitated by the monoamine oxidase inhibitor linezolid. American Journal of Psychiatry 164, 346-347.
57. Palm F, Mossner R, Chen Y, He L, Gerlach M, Bischofs S, Riederer P, Lesch KP, Sommer C (2008). Reduced thermal hyperalgesia and enhanced peripheral nerve injury after hind paw inflammation in mice lacking the serotonin-transporter. European Journal of Pain 12, 790-797.
58. Parker V, Wong AH, Boon HS, Seeman MV (2001). Adverse reactions to St John's Wort. Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie 46, 77-79.
59. Prasad HC, Zhu CB, McCauley JL, Samuvel DJ, Ramamoorthy S, Shelton RC, Hewlett WA, Sutcliffe JS, Blakely RD (2005). Human serotonin transporter variants display altered sensitivity to protein kinase G and p38 mitogen-activated protein kinase. Proceedings of the National Academy of Sciences USA 102, 11545-11550.
60. Praschak-Rieder N, Kennedy J, Wilson AA, Hussey D, Boovariwala A, Willeit M, Ginovart N, Tharmalingam S, Masellis M, Houle S, Meyer JH (2007). Novel 5-HTTLPR allele associates with higher serotonin transporter binding in putamen: a [(11)C] DASB positron emission tomography study. Biological Psychiatry 62, 327-331.
61. Qu Y, Villacreses N, Murphy DL, Rapoport SI (2005). 5-HT2A/2C receptor signaling via phospholipase A2 and arachidonic acid is attenuated in mice lacking the serotonin reuptake transporter. Psychopharmacology 180, 12-20.
62. Raffa RB, Friderichs E, Reimann W, Shank RP, Codd EE, Vaught JL (1992). Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an 'atypical' opioid analgesic. Journal of Pharmacology and Experimental Therapeutics 260, 275-285.
63. Reeves RR, Cox SK (2008). Similar effects of tramadol and venlafaxine in major depressive disorder. Southern Medical Journal 101, 193-195.
64. Ringland C, Mant A, McGettigan P, Mitchell P, Kelman C, Buckley N, Pearson SA (2008). Uncovering the potential risk of serotonin toxicity in Australian veterans using pharmaceutical claims data. British Journal of Clinical Pharmacology 66, 682-688.
65. Rioux A, Fabre V, Lesch KP, Moessner R, Murphy DL, Lanfumey L, Hamon M, Martres MP (1999). Adaptive changes of serotonin 5-HT2A receptors in mice lacking the serotonin transporter. Neuroscience Letters 262, 113-116.
66. Rojas-Corrales MO, Berrocoso E, Gibert-Rahola J, Mico JA (2002). Antidepressant-like effects of tramadol and other central analgesics with activity on monoamines reuptake, in helpless rats. Life Sciences 72, 143-152.
67. Rojas-Corrales MO, Berrocoso E, Gibert-Rahola J, Mico JA (2004). Antidepressant-like effect of tramadol and its enantiomers in reserpinized mice: comparative study with desipramine, fluvoxamine, venlafaxine and opiates. Journal of Psychopharmacology 18, 404-411.
68. Rojas-Corrales MO, Berrocoso E, Mico JA (2005). Role of 5-HT1A and 5-HT1B receptors in the antinociceptive effect of tramadol. European Journal of Pharmacology 511, 21-26.
69. Rojas-Corrales MO, Gibert-Rahola J, Mico JA (1998). Tramadol induces antidepressant-type effects in mice. Life Sciences 63, PL175-180.
70. Rojas-Corrales MO, Gibert-Rahola J, Mico JA (2007). Role of atypical opiates in OCD. Experimental approach through the study of 5-HT(2A/C) receptor-mediated behavior. Psychopharmacology 190, 221-231.
71. Rojas-Corrales MO, Ortega-Alvaro A, Gibert-Rahola J, Roca-Vinardell A, Mico JA (2000). Pindolol, a beta-adrenoceptor blocker/5-hydroxytryptamine(1A/1B) antagonist, enhances the analgesic effect of tramadol. Pain 88, 119-124.
72. Shapira NA, Keck Jr. P.E., Goldsmith TD, McConville BJ, Eis M, McElroy SL (1997a). Open-label pilot study of tramadol hydrochloride in treatment-refractory obsessive-compulsive disorder. Depression and Anxiety 6, 170-173.
73. Shapira NA, McConville BJ, Pagnucco ML, Norman AB, Keck Jr. P.E. (1997b). Novel use of tramadol hydrochloride in the treatment of Tourette's syndrome. Journal of Clinical Psychiatry 58, 174-175.
74. Shapira NA, Verduin ML, DeGraw JD (2001). Treatment of refractory major depression with tramadol monotherapy. Journal of Clinical Psychiatry 62, 205-206.
75. Smith LM, Peroutka SJ (1986). Differential effects of 5-hydroxytryptamine1a selective drugs on the 5-HT behavioral syndrome. Pharmacology, Biochemistry and Behavior 24, 1513-1519.
76. Spencer C (2000). The efficacy of intramuscular tramadol as a rapid-onset antidepressant. Australian and New Zealand Journal of Psychiatry 34, 1032-1033.
77. Sternbach H (1991). The serotonin syndrome. American Journal of Psychiatry 148, 705-713.
78. Sun HL, Zheng JW, Wang K, Liu RK, Liang JH (2003). Tramadol reduces the 5-HTP-induced head-twitch response in mice via the activation of mu and kappa opioid receptors. Life Sciences 72, 1221-1230.
79. Tissot TA (2003). Probable meperidine-induced serotonin syndrome in a patient with a history of fluoxetine use. Anesthesiology 98, 1511-1512.
80. Vizcaychipi MP, Walker S, Palazzo M (2007). Serotonin syndrome triggered by tramadol. British Journal of Anaesthesia 99, 919.
81. Xie H, Dong ZQ, Ma F, Bauer WR, Wang X, Wu GC (2008). Involvement of serotonin 2A receptors in the analgesic effect of tramadol in mono-arthritic rats. Brain Research 1210, 76-83.
82. Yalcin I, Aksu F, Belzung C (2005). Effects of desipramine and tramadol in a chronic mild stress model in mice are altered by yohimbine but not by pindolol. European Journal of Pharmacology 514, 165-174.
83. Yalcin I, Aksu F, Bodard S, Chalon S, Belzung C (2007). Antidepressant-like effect of tramadol in the unpredictable chronic mild stress procedure: possible involvement of the noradrenergic system. Behavioural Pharmacology 18, 623-631.
84. Yalcin I, Coubard S, Bodard S, Chalon S, Belzung C (2008). Effects of 5,7-dihydroxytryptamine lesion of the dorsal raphe nucleus on the antidepressant-like action of tramadol in the unpredictable chronic mild stress in mice. Psychopharmacology 200, 497-507.
85. Yamada J, Sugimoto Y, Horisaka K (1988). The behavioural effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in mice. European Journal of Pharmacology 154, 299-304.