Increased interleukin-1β levels following low dose MDMA induces tolerance against the 5-HT neurotoxicity produced by challenge MDMA

Journal of Neuroinflammation

Esther O'Shea¹  Maria I Colado¹  Maria D Gutierrez-Lopez¹  Elisa Torres¹  Andrea Mayado¹ 

[1] Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain

关键词: 5-HT;    neurotoxicity;    sIL-1RI;    IL-1ra;    IL-1β;    tolerance;    preconditioning;    MDMA;   

Others  :  1212986
DOI  :  10.1186/1742-2094-8-165

 received in 2011-09-20, accepted in 2011-11-24,  发布年份 2011

【 摘 要 】

Background

Preconditioning is a phenomenon by which tolerance develops to injury by previous exposure to a stressor of mild severity. Previous studies have shown that single or repeated low dose MDMA can attenuate 5-HT transporter loss produced by a subsequent neurotoxic dose of the drug. We have explored the mechanism of delayed preconditioning by low dose MDMA.

Methods

Male Dark Agouti rats were given low dose MDMA (3 mg/kg, i.p.) 96 h before receiving neurotoxic MDMA (12.5 mg/kg, i.p.). IL-1β and IL1ra levels and 5-HT transporter density in frontal cortex were quantified at 1 h, 3 h or 7 days. IL-1β, IL-1ra and IL-1RI were determined between 3 h and 96 h after low dose MDMA. sIL-1RI combined with low dose MDMA or IL-1β were given 96 h before neurotoxic MDMA and toxicity assessed 7 days later.

Results

Pretreatment with low dose MDMA attenuated both the 5-HT transporter loss and elevated IL-1β levels induced by neurotoxic MDMA while producing an increase in IL-1ra levels. Low dose MDMA produced an increase in IL-1β at 3 h and in IL-1ra at 96 h. sIL-1RI expression was also increased after low dose MDMA. Coadministration of sIL-1RI (3 μg, i.c.v.) prevented the protection against neurotoxic MDMA provided by low dose MDMA. Furthermore, IL-1β (2.5 pg, intracortical) given 96 h before neurotoxic MDMA protected against the 5-HT neurotoxicity produced by the drug, thus mimicking preconditioning.

Conclusions

These results suggest that IL-1β plays an important role in the development of delayed preconditioning by low dose MDMA.

【 授权许可】

   
2011 Mayado et al; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Green AR, Mechan AO, Elliott JM, O'Shea E, Colado MI: The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"). Pharmacol Rev 2003, 55:463-508.
• [2]Commins DL, Vosmer G, Virus RM, Woolverton WL, Schuster CR, Seiden LS: Biochemical and histological evidence that methylenedioxymethylamphetamine (MDMA) is toxic to neurons in the rat brain. J Pharmacol Exp Ther 1987, 241:338-345.
• [3]O'Hearn E, Battaglia G, De Souza EB, Kuhar MJ, Molliver ME: Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity. J Neurosci 1988, 8:2788-2803.
• [4]Colado MI, O'Shea E, Granados R, Murray TK, Green AR: In vivo evidence for free radical involvement in the degeneration of rat brain 5-HT following administration of MDMA ('ecstasy') and p-chloroamphetamine but not the degeneration following fenfluramine. Br J Pharmacol 1997, 121:889-900.
• [5]O'Shea E, Granados R, Esteban B, Colado MI, Green AR: The relationship between the degree of neurodegeneration of rat brain 5-HT nerve terminals and the dose and frequency of administration of MDMA ('ecstasy'). Neuropharmacology 1998, 37:919-926.
• [6]Hewitt KE, Green AR: Chlormethiazole, dizocilpine and haloperidol prevent the degeneration of serotonergic nerve terminals induced by administration of MDMA ('Ecstasy') to rats. Neuropharmacology 1994, 33:1589-1595.
• [7]Sharkey J, McBean DE, Kelly PA: Alterations in hippocampal function following repeated exposure to the amphetamine derivative methylenedioxymethamphetamine ("Ecstasy"). Psychopharmacology (Berl) 1991, 105:113-118.
• [8]O'Shea E, Orio L, Escobedo I, Sanchez V, Camarero J, Green AR, Colado MI: MDMA-induced neurotoxicity: long-term effects on 5-HT biosynthesis and the influence of ambient temperature. Br J Pharmacol 2006, 148:778-785.
• [9]Orio L, O'Shea E, Sanchez V, Pradillo JM, Escobedo I, Camarero J, Moro MA, Green AR, Colado MI: 3,4-Methylenedioxymethamphetamine increases interleukin-1beta levels and activates microglia in rat brain: studies on the relationship with acute hyperthermia and 5-HT depletion. J Neurochem 2004, 89:1445-1453.
• [10]O'Shea E, Sanchez V, Orio L, Escobedo I, Green AR, Colado MI: 3,4-Methylenedioxymethamphetamine increases pro-interleukin-1beta production and caspase-1 protease activity in frontal cortex, but not in hypothalamus, of Dark Agouti rats: role of interleukin-1beta in neurotoxicity. Neuroscience 2005, 135:1095-1105.
• [11]Janoff A: Alterations in lysosomes (intracellular enzymes) during shock; effects of preconditioning (tolerance) and protective drugs. Int Anesthesiol Clin 1964, 2:251-269.
• [12]Barone FC, White RF, Spera PA, Ellison J, Currie RW, Wang X, Feuerstein GZ: Ischemic preconditioning and brain tolerance: temporal histological and functional outcomes, protein synthesis requirement, and interleukin-1 receptor antagonist and early gene expression. Stroke 1998, 29:1937-1950.
• [13]Escobedo I, Peraile I, Orio L, Colado MI, O'Shea E: Evidence for a role of Hsp70 in the neuroprotection induced by heat shock pre-treatment against 3,4-methylenedioxymethamphetamine toxicity in rat brain. J Neurochem 2007, 101:1272-1283.
• [14]Kitagawa K, Matsumoto M, Kuwabara K, Tagaya M, Ohtsuki T, Hata R, Ueda H, Handa N, Kimura K, Kamada T: 'Ischemic tolerance' phenomenon detected in various brain regions. Brain Res 1991, 561:203-211.
• [15]Omata N, Murata T, Takamatsu S, Maruoka N, Yonekura Y, Fujibayashi Y, Wada Y: Region-specific induction of hypoxic tolerance by expression of stress proteins and antioxidant enzymes. Neurol Sci 2006, 27:74-77.
• [16]Wang CH, Chang A, Tsai MJ, Cheng H, Liao LP, Lin AM: Kainic acid-induced oxidative injury is attenuated by hypoxic preconditioning. Ann N Y Acad Sci 2005, 1042:314-324.
• [17]Obrenovitch TP: Molecular physiology of preconditioning-induced brain tolerance to ischemia. Physiol Rev 2008, 88:211-247.
• [18]Lastres-Becker I, Cartmell T, Molina-Holgado F: Endotoxin preconditioning protects neurones from in vitro ischemia: role of endogenous IL-1beta and TNF-alpha. J Neuroimmunol 2006, 173:108-116.
• [19]Shin JA, Park EM, Choi JS, Seo SM, Kang JL, Lee KE, Cho S: Ischemic preconditioning-induced neuroprotection is associated with differential expression of IL-1beta and IL-1 receptor antagonist in the ischemic cortex. J Neuroimmunol 2009, 217:14-19.
• [20]Bhide NS, Lipton JW, Cunningham JI, Yamamoto BK, Gudelsky GA: Repeated exposure to MDMA provides neuroprotection against subsequent MDMA-induced serotonin depletion in brain. Brain Res 2009, 1286:32-41.
• [21]Mayado A, Torres E, Peraile I, Izco M, Gutierrez-Lopez MD, Colado MI, O'Shea E: Repeated low dose MDMA protects against a subsequent neurotoxic dose of MDMA and reduces IL-1β release [abstract]. Fundamental & Clinical Pharmacology 2008, 22(S2):P139.
• [22]Murakami N, Sakata Y, Watanabe T: Central actions sites of interleukin-1 beta for inducing fever in rabbits. J Physiol 1990, 428:299-312.
• [23]Gery I, Gershon RK, Waksman BH: Potentiation of the T-lymphocyte response to mitogens. I. The responding cell. J Exp Med 1972, 136:128-142.
• [24]Greenfeder SA, Nunes P, Kwee L, Labow M, Chizzonite RA, Ju G: Molecular cloning and characterization of a second subunit of the interleukin-1 receptor complex. J Biol Chem 1995, 270:13757-13765.
• [25]Dinarello CA: Interleukin-1. Cytokine Growth Factor Rev 1997, 8:253-265.
• [26]Colado MI, O'Shea E, Granados R, Esteban B, Martín AB, Green AR: Studies on the role of dopamine in the degeneration of 5-HT nerve endings in the brain of Dark Agouti rats following 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') administration. Br J Pharmacol 1999, 126:911-924.
• [27]König JFR, Klippel RA: The Rat Brain. A Stereotaxic Atlas of the Forebrain and Lower Parts of the Brain Stem. New York, Robert E Krieger Publishing Co. Inc; 1963.
• [28]Baldwin HA, Williams JL, Snares M, Ferreira T, Cross AJ, Green AR: Attenuation by chlormethiazole administration of the rise in extracellular amino acids following focal ischaemia in the cerebral cortex of the rat. Br J Pharmacol 1994, 112:188-194.
• [29]Wang X, Baumann MH, Xu H, Morales M, Rothman RB: (+/-)-3,4-Methylenedioxymethamphetamine administration to rats does not decrease levels of the serotonin transporter protein or alter its distribution between endosomes and the plasma membrane. J Pharmacol Exp Ther 2005, 314:1002-1012.
• [30]Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976, 72:248-254.
• [31]Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 1951, 193:265-275.
• [32]Torres E, Gutierrez-Lopez MD, Borcel E, Peraile I, Mayado A, O'Shea E, Colado MI: Evidence that MDMA ('ecstasy') increases cannabinoid CB2 receptor expression in microglial cells: role in the neuroinflammatory response in rat brain. J Neurochem 2010, 113:67-78.
• [33]Torres E, Gutierrez-Lopez MD, Mayado A, Rubio A, O'Shea E, Colado MI: Changes in interleukin-1 signal modulators induced by 3,4-methylenedioxymethamphetamine (MDMA): regulation by CB2 receptors and implications for neurotoxicity. J Neuroinflammation 2011, 8:53. BioMed Central Full Text
• [34]Dirnagl U, Simon RP, Hallenbeck JM: Ischemic tolerance and endogenous neuroprotection. Trends Neurosci 2003, 26:248-254.
• [35]Piper BJ, Vu HL, Safain MG, Oliver AJ, Meyer JS: Repeated adolescent 3,4-methylenedioxymethamphetamine (MDMA) exposure in rats attenuates the effects of a subsequent challenge with MDMA or a 5-hydroxytryptamine(1A) receptor agonist. J Pharmacol Exp Ther 2006, 317:838-849.
• [36]Piper BJ, Ali SF, Daniels LG, Meyer JS: Repeated intermittent methylenedioxymethamphetamine exposure protects against the behavioral and neurotoxic, but not hyperthermic, effects of an MDMA binge in adult rats. Synapse 2010, 64:421-431.
• [37]Green AR, O'Shea E, Colado MI: A review of the mechanisms involved in the acute MDMA (ecstasy)-induced hyperthermic response. Eur J Pharmacol 2004, 500:3-13.
• [38]Sanchez V, O'Shea E, Saadat KS, Elliott JM, Colado MI, Green AR: Effect of repeated ('binge') dosing of MDMA to rats housed at normal and high temperature on neurotoxic damage to cerebral 5-HT and dopamine neurones. J Psychopharmacol 2004, 18:412-416.
• [39]Orio L, Llopis N, Torres E, Izco M, O'Shea E, Colado MI: A study on the mechanisms by which minocycline protects against MDMA ('ecstasy')-induced neurotoxicity of 5-HT cortical neurons. Neurotox Res 2010, 18:187-99.
• [40]Dinarello CA, Thompson RC: Blocking IL-1: interleukin 1 receptor antagonist in vivo and in vitro. Immunol Today 1991, 12:404-410.
• [41]Allan SM, Rothwell NJ: Cytokines and acute neurodegeneration. Nat Rev Neurosci 2001, 2:734-744.
• [42]Martin D, Chinookoswong N, Miller G: The interleukin-1 receptor antagonist (rhIL-1ra) protects against cerebral infarction in a rat model of hypoxia-ischemia. Exp Neurol 1995, 130:362-367.
• [43]Relton JK, Rothwell NJ: Interleukin-1 receptor antagonist inhibits ischaemic and excitotoxic neuronal damage in the rat. Brain Res Bull 1992, 29:243-246.
• [44]Stroemer RP, Rothwell NJ: Cortical protection by localized striatal injection of IL-1ra following cerebral ischemia in the rat. J Cereb Blood Flow Metab 1997, 17:597-604.
• [45]Loddick SA, Wong ML, Bongiorno PB, Gold PW, Licinio J, Rothwell NJ: Endogenous interleukin-1 receptor antagonist is neuroprotective. Biochem Biophys Res Commun 1997, 234:211-215.
• [46]Josephs MD, Solorzano CC, Taylor M, Rosenberg JJ, Topping D, Abouhamze A, Mackay SL, Hirsch E, Hirsh D, Labow M, Moldawer LL: Modulation of the acute phase response by altered expression of the IL-1 type 1 receptor or IL-1ra. Am J Physiol Regul Integr Comp Physiol 2000, 278:R824-830.
• [47]Molina-Holgado F, Pinteaux E, Moore JD, Molina-Holgado E, Guaza C, Gibson RM, Rothwell NJ: Endogenous interleukin-1 receptor antagonist mediates anti-inflammatory and neuroprotective actions of cannabinoids in neurons and glia. J Neurosci 2003, 23:6470-6474.
• [48]Rothwell NJ, del Zoppo GJ: Editorial comment to Barone et al. Stroke. 1998, 29:1950-1951.
• [49]Sims JE, Giri JG, Dower SK: The two interleukin-1 receptors play different roles in IL-1 actions. Clin Immunol Immunopathol 1994, 72:9-14.
• [50]Blondeau N, Widmann C, Lazdunski M, Heurteaux C: Activation of the nuclear factor-kappaB is a key event in brain tolerance. J Neurosci 2001, 21:4668-4677.
• [51]Ohtsuki T, Ruetzler CA, Tasaki K, Hallenbeck JM: Interleukin-1 mediates induction of tolerance to global ischemia in gerbil hippocampal CA1 neurons. J Cereb Blood Flow Metab 1996, 16:1137-1142.