Abstract
The mechanisms of action of the rapid antidepressant effects of ketamine, an N-methyl-D-aspartate glutamate receptor antagonist, have not been fully elucidated. This study examined the effects of ketamine on ligand binding to a metabotropic glutamatergic receptor (mGluR5) in individuals with major depressive disorder (MDD) and healthy controls. Thirteen healthy and 13 MDD nonsmokers participated in two [11C]ABP688 positron emission tomography (PET) scans on the same day—before and during intravenous ketamine administration—and a third scan 1 day later. At baseline, significantly lower [11C]ABP688 binding was detected in the MDD as compared with the control group. We observed a significant ketamine-induced reduction in mGluR5 availability (that is, [11C]ABP688 binding) in both MDD and control subjects (average of 14±9% and 19±22%, respectively; P<0.01 for both), which persisted 24 h later. There were no differences in ketamine-induced changes between MDD and control groups at either time point (P=0.8). A significant reduction in depressive symptoms was observed following ketamine administration in the MDD group (P<0.001), which was associated with the change in binding (P<0.04) immediately after ketamine. We hypothesize that glutamate released after ketamine administration moderates mGluR5 availability; this change appears to be related to antidepressant efficacy. The sustained decrease in binding may reflect prolonged mGluR5 internalization in response to the glutamate surge.
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References
Global Burden of Disease Study Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015; 386: 743–800.
World Health Organization The Global Burden of Disease: 2004 Update, Table A2: Burden of Disease in DALYs by Cause, Sex and Income Group in WHO Regions, Estimates for 2004. WHO: Geneva, Switzerland, 2008; http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_AnnexA.pdf.
McClintock S, Husain M, Wisniewski S, Nierenberg A, Stewart J, Trivedi M et al. Residual symptoms in depressed outpatients who respond by 50% but do not remit to antidepressant medication. J Clin Psychopharmacol 2011; 31: 180–186.
Zisook S, Ganadjian K, Moutier C, Prather R, Rao S . Sequenced Treatment Alternatives to Relieve Depression (STAR*D): lessons learned. J Clin Psychiatry 2008; 69: 1184–1185.
Krystal J, Mathew S, D'Souza D, Garakani A, Gunduz-Bruce H, Charney D . Potential psychiatric applications of metabotropic glutamate receptor agonists and antagonists. CNS Drugs 2010; 24: 669–693.
Krystal J, Sanacora G, Duman R . Rapid-acting glutamatergic antidepressants: the path to ketamine and beyond. Biol Psychiatry 2013; 73: 1133–1141.
Sanacora G, Zarate CAJ, Krystal JH, Manji HK . Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nat Rev Drug Discov 2008; 7: 426–437.
Hashimoto K, Sawa A, Iyo M . Increased levels of glutamate in brains from patients with mood disorders. Biol Psychiatry 2007; 62: 1310–1316.
Abdallah C, Mason G, DellaGioia N, Sanacora G, Jiang L, Matuskey D et al. mGluR5 and glutamate involvement in MDD: a multimodal imaging study. Biol Psychiatry, (under review).
Sanacora G, Gueorguieva R, Epperson C, Wu Y-T, Appel M, Rothman D et al. Subtype-specific alterations of GABA and glutamate in major depression. Arch Gen Psychiatry 2004; 61: 705–713.
DeLorenzo C, DellaGioia N, Bloch M, Sanacora G, Nabulsi N, Abdallah C et al. In vivo ketamine-induced changes in [11C]ABP688 binding to metabotropic glutamate receptor subtype 5. Biol Psychiatry 2015; 77: 266–275.
Miyake N, Skinbjerg M, Easwaramoorthy B, Kumar D, Girgis R, Xu X et al. Imaging changes in glutamate transmission in vivo with the metabotropic glutamate receptor 5 tracer [11C] ABP688 and N-acetylcysteine challenge. Biol Psychiatry 2011; 69: 822–824.
Luykx J, Laban K, Heuvel Mvd, Boks M, Mandl R, Kahn R et al. Region and state specific glutamate downregulation in major depressive disorder: a meta-analysis of (1)H-MRS findings. Neurosci Biobehav Rev 2012; 36: 198–205.
Hasler G, Veen Jvd, Tumonis T, Meyers N, Shen J, Drevets W . Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy. Arch Gen Psychiatry 2007; 64: 193–200.
Sistiaga A, Herrero I, Conquet F, Sánchez-Prieto J . The metabotropic glutamate receptor 1 is not involved in the facilitation of glutamate release in cerebrocortical nerve terminals. Neuropharmacology 1998; 37: 1485–1492.
Manahan-Vaughan D, Braunewell K . Novelty acquisition is associated with induction of hippocampal long-term depression. Proc Natl Acad Sci USA 1999; 96: 8739–8744.
Shigemoto R, Kinoshita A, Wada E, Nomura S, Ohishi H, Takada M et al. Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus. J Neurosci 1997; 17: 7503–7522.
Takumi Y, Matsubara A, Rinvik E, Ottersen O . The arrangement of glutamate receptors in excitatory synapses. Ann NY Acad Sci 1999; 868: 474–482.
Hubert G, Paquet M, Smith Y . Differential subcellular localization of mGluR1a and mGluR5 in the rat and monkey substantia nigra. J Neurosci 2001; 21: 1838–1847.
López-Bendito G, Shigemoto R, Fairén A, Luján R . Differential distribution of group I metabotropic glutamate receptors during rat cortical development. Cereb Cortex 2002; 12: 625–638.
O'Malley K, Jong Y, Gonchar Y, Burkhalter A, Romano C . Activation of metabotropic glutamate receptor mGlu5 on nuclear membranes mediates intranuclear Ca2+ changes in heterologous cell types and neurons. J Biol Chem 2003; 278: 28210–28219.
Shin S, Kwon O, Kang JI, Kwon S, Oh S, Choi J et al. mGluR5 in the nucleus accumbens is critical for promoting resilience to chronic stress. Nat Neurosci 2015; 18: 1017–1024.
Kovacevic T, Skelin I, Minuzzi L, Rosa-Neto P, Diksic M . Reduced metabotropic glutamate receptor 5 in the Flinders Sensitive Line of rats, an animal model of depression: an autoradiographic study. Brain Res Bull 2012; 87: 406–412.
Wieronska JM, Branski P, Szewczyk B, Palucha A, Papp M, Gruca P et al. Changes in the expression of metabotropic glutamate receptor 5 (mGluR5) in the rat hippocampus in an animal model of depression. Pol J Pharmacol 2001; 53: 659–662.
Fatemi SH, Folsom TD, Rooney RJ, Thuras PD . mRNA and protein expression for novel GABAA receptors theta and rho2 are altered in schizophrenia and mood disorders; relevance to FMRP-mGluR5 signaling pathway. Transl Psychiatry 2013; 3: e271.
Deschwanden A, Karolewicz B, Feyissa AM, Treyer V, Ametamey SM, Johayem A et al. Reduced metabotropic glutamate receptor 5 density in major depression determined by [(11)C]ABP688 PET and postmortem study. Am J Psychiatry 2011; 168: 727–734.
Matosin N, Fernandez-Enright F, Frank E, Deng C, Wong J, Huang XF et al. Metabotropic glutamate receptor mGluR2/3 and mGluR5 binding in the anterior cingulate cortex in psychotic and nonpsychotic depression, bipolar disorder and schizophrenia: implications for novel mGluR-based therapeutics. J Psychiatry Neurosci 2014; 39: 407–416.
Smialowska M, Szewczyk B, Branski P, Wieronska JM, Palucha A, Bajkowska M et al. Effect of chronic imipramine or electroconvulsive shock on the expression of mGluR1a and mGluR5a immunoreactivity in rat brain hippocampus. Neuropharmacology 2002; 42: 1016–1023.
Berman R, Cappiello A, Anand A, Oren D, Heninger G, Charney D et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 2000; 47: 351–354.
Abdallah C, Adams T, Kelmendi B, Esterlis I, Sanacora G, Krystal J . Ketamine's mechanism of action: a path to rapid-acting antidepressants. Depress Anxiety 2016; 33: 689–697.
Chowdhury G, Behar K, Cho W, Thomas M, Rothman D, Sanacora G . ¹H-[¹3C]-nuclear magnetic resonance spectroscopy measures of ketamine's effect on amino acid neurotransmitter metabolism. Biol Psychiatry 2012; 71: 1022–1025.
Chowdhury G, Zhang J, Thomas M, Banasr M, Ma X, Pittman B et al. Transiently increased glutamate cycling in rat PFC is associated with rapid onset of antidepressant-like effects. Mol Psychiatry 2016; 22: 120–126.
Montgomery SA, Asberg M . A new depression scale designed to be sensitive to change. Br J Psychiatry 1979; 134: 382–389.
Beck S, Ward C, Mendelsohn M, Erbaugh J . An inventory for measuring depression. Arch Gen Psychiatry 1961; 4: 561–571.
Bremner J, Krystal J, Putnam F, Southwick S, Marmar C, Charney D et al. Measurement of dissociative states with the Clinician-Administered Dissociative States Scale (CADSS). J Trauma Stress 1999; 11: 125–136.
Norcross J, Guadagnoli E, Prochaska J . Factor structure of the profile of mood states (POMs), two partial replications. J Clin Psychol 1984; 40: 1270–1277.
Sandiego CM, Nabulsi N, Lin SF, Labaree D, Najafzadeh S, Huang Y et al. Studies of the metabotropic glutamate receptor 5 radioligand [(1)(1)C]ABP688 with N-acetylcysteine challenge in rhesus monkeys. Synapse 2013; 67: 489–501.
Kawamura K, Yamasaki T, Kumata K, Furutsuka K, Takei M, Wakizaka H et al. Binding potential of (E)-[(11)C]ABP688 to metabotropic glutamate receptor subtype 5 is decreased by the inclusion of its (11)C-labelled Z-isomer. Nucl Med Biol 2014; 41: 17–23.
Anticevic A, Gancsos M, Murray J, Repovs G, Driesen N, Ennis D et al. NMDA receptor function in large-scale anti-correlated neural systems with implications for cognition and schizophrenia. Proc Natl Acad Sci 2012; 109: 16720–16725.
Driesen NR, McCarthy G, Bhagwagar Z, Bloch M, Calhoun V, D'Souza DC et al. Relationship of resting brain hyperconnectivity and schizophrenia-like symptoms produced by the NMDA receptor antagonist ketamine in humans. Mol Psychiatry 2013; 18: 1199–1204.
Ametamey S, Kessler L, Honer M, Wyss M, Buck A, Hintermann S et al. Radiosynthesis and preclinical evaluation of 11C-ABP688 as a probe for imaging the metabotropic glutamate receptor subtype 5. J Nucl Med 2006; 47: 698–705.
Rusjan PM, Wilson AA, Bloomfield PM, Vitcu I, Meyer JH, Houle S et al. Quantitation of translocator protein binding in human brain with the novel radioligand [18F]-FEPPA and positron emission tomography. J Cereb Blood Flow Metab 2011; 31: 1807–1816.
Gallezot JD, Nabulsi N, Neumeister A, Planeta-Wilson B, Williams WA, Singhal T et al. Kinetic modeling of the serotonin 5-HT(1B) receptor radioligand [(11)C]P943 in humans. J Cereb Blood Flow Metab 2010; 30: 196–210.
Wu S, Ogden RT, Mann JJ, Parsey RV . Optimal metabolite curve fitting for kinetic modeling of 11C-WAY-100635. J Nucl Med 2007; 48: 926–931.
DeLorenzo C, Milak MS, Brennan KG, Kumar JS, Mann JJ, Parsey RV . In vivo positron emission tomography imaging with [(11)C]ABP688: binding variability and specificity for the metabotropic glutamate receptor subtype 5 in baboons. Eur J Nucl Med Mol Imaging 2011; 38: 1083–1094.
DeLorenzo C, Kumar JS, Mann JJ, Parsey RV . In vivo variation in metabotropic glutamate receptor subtype 5 binding using positron emission tomography and [11C]ABP688. J Cereb Blood Flow Metab 2011; 31: 2169–2180.
DeLorenzo C, Klein A, Mikhno A, Gray N, Zanderigo F, Mann JJ et al A New Method for Assessing PET-MRI Coregistration. Proceedings of SPIE; 7 February 2009; Lake Buena Vista, Florida, USA.
Treyer V, Streffer J, Wyss MT, Bettio A, Ametamey SM, Fischer U et al. Evaluation of the metabotropic glutamate receptor subtype 5 using PET and 11C-ABP688: assessment of methods. J Nucl Med 2007; 48: 1207–1215.
Patel S, Hamill T, Connolly B, Jagoda E, Li W, Gibson R . Species differences in mGluR5 binding sites in mammalian central nervous system determined using in vitro binding with [18F]F-PEB. Nucl Med Biol 2007; 34: 1009–1017.
Innis RB, Cunningham VJ, Delforge J, Fujita M, Gjedde A, Gunn RN et al. Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab 2007; 27: 1533–1539.
Hirvonen J, Johansson J, Teras M, Oikonen V, Lumme V, Virsu P et al. Measurement of striatal and extrastriatal dopamine transporter binding with high-resolution PET and [11C]PE2I: quantitative modeling and test-retest reproducibility. J Cereb Blood Flow Metab 2008; 28: 1059–1069.
Parker R, Flint E, Bosworth H, Pieper C, Steffens D . A three-factor analytic model of the MADRS in geriatric depression. Int J Geriatr Psychiatry 2003; 18: 73–77.
Huang C, Chen J . Meta-analysis of the factor structures of the Beck Depression Inventory-II. Assessment 2015; 22: 459–472.
Moghaddam B, Adams B, Verma A, Daly D . Activation of glutamatergic neurotransmission by ketamine: a novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex. J Neurosci 1997; 17: 2921–2927.
Zanos P, Moaddel R, Morris PJ, Georgiou P, Fischell J, Elmer GI et al. NMDAR inhibition-independent antidepressant actions of ketamine metabolites. Nature 2016; 533: 481–486.
Duman R, Aghajanian G, Sanacora G, Krystal J . Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants. Nat Med 2016; 22: 238–249.
Kim H, Lee K, Lee D, Han Y, Lee S, Sohn J et al. Costimulation of AMPA and metabotropic glutamate receptors underlies phospholipase C activation by glutamate in hippocampus. J Neurosci 2015; 35: 6401–6412.
Lorrain D, Baccei C, Bristow L, Anderson J, Varney M . Effects of ketamine and N-methyl-D-aspartate on glutamate and dopamine release in the rat prefrontal cortex: modulation by a group II selective metabotropic glutamate receptor agonist LY379268. Neuroscience 2003; 117: 697–706.
Bartolomeis Ad, Sarappa C, Buonaguro E, Marmo F, Eramo A, Tomasetti C et al. Different effects of the NMDA receptor antagonists ketamine, MK-801, and memantine on postsynaptic density transcripts and their topography: role of Homer signaling, and implications for novel antipsychotic and pro-cognitive targets in psychosis. Prog Neuropsychopharmacol Biol Psychiatry 2013; 46: 1–12.
DeLorenzo C, Kumar JD, Mann J, Parsey R . In vivo variation in metabotropic glutamate receptor subtype 5 binding using positron emission tomography and [11C]ABP688. J Cereb Blood Flow Metab 2011; 31: 2169–2180.
DeLorenzo C, Gallezot J, Gardus J, Yang J, Planeta B, Nabulsi N et al. In vivo variation in same-day estimates of metabotropic glutamate receptor subtype 5 binding using [11C]ABP688 and [18F]FPEB JCBFM. J Cereb Blood Flow Metab 2016 (e-pub ahead of print).
Attwell D, Buchan AM, Charpak S, Lauritzen M, Macvicar BA, Newman EA . Glial and neuronal control of brain blood flow. Nature 2010; 468: 232–243.
Kågedal M, Cselényi Z, Nyberg S, Raboisson P, Ståhle L, Stenkrona P et al. A positron emission tomography study in healthy volunteers to estimate mGluR5 receptor occupancy of AZD2066 - estimating occupancy in the absence of a reference region. Neuroimage 2013; 82: 160–169.
Abdallah C, Sanacora G, Duman R, Krystal J . Ketamine and rapid-acting antidepressants: a window into a new neurobiology for mood disorder therapeutics. Annu Rev Med 2015; 66: 509–523.
Li N, Lee B, Liu R, Banasr M, Dwyer J, Iwata M et al. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 2010; 329: 959–964.
Pałucha A, Brański P, Szewczyk B, Wierońska J, Kłak K, Pilc A . Potential antidepressant-like effect of MTEP, a potent and highly selective mGluR5 antagonist. Pharmacol Biochem Behav 2005; 81: 901–906.
Tatarczyńska E, Klodzińska A, Chojnacka-Wójcik E, Palucha A, Gasparini F, Kuhn R et al. Potential anxiolytic- and antidepressant-like effects of MPEP, a potent, selective and systemically active mGlu5 receptor antagonist. Br J Pharmacol 2001; 132: 1423–1430.
Pałucha-Poniewiera A, Wierońska J, Brański P, Burnat G, Chruścicka B, Pilc A . Is the mGlu5 receptor a possible target for new antidepressant drugs? Pharmacol Rep 2013; 65: 1506–1511.
Quiroz JA, Tamburri P, Deptula D, Banken L, Beyer U, Rabbia M et al. Efficacy and safety of basimglurant as adjunctive therapy for major depression: a randomized clinical trial. JAMA Psychiatry 2016; 73: 675–684.
Iijima M, Fukumoto K, Chaki S . Acute and sustained effects of a metabotropic glutamate 5 receptor antagonist in the novelty-suppressed feeding test. Behav Brain Res 2012; 235: 287–292.
Fontanez-Nuin D, Santini E, Quirk G, Porter J . Memory for fear extinction requires mGluR5-mediated activation of infralimbic neurons. Cereb Cortex 2011; 21: 727–735.
Chen L, Liu J, Ali U, Gui Z, Hou C, Fan L et al. Chronic, systemic treatment with a metabotropic glutamate receptor 5 antagonist produces anxiolytic-like effects and reverses abnormal firing activity of projection neurons in the basolateral nucleus of the amygdala in rats with bilateral 6-OHDA lesions. Brain Res Bull 2011; 84: 215–223.
Molina-Hernández M, Tellez-Alcántara N, Pérez-García J, Olivera-Lopez J, Jaramillo M . Antidepressant-like and anxiolytic-like actions of the mGlu5 receptor antagonist MTEP, microinjected into lateral septal nuclei of male Wistar rats. Prog Neuropsychopharmacol Biol Psychiatry 2006; 30: 1129–1135.
Mora MPdl, Lara-García D, Jacobsen K, Vázquez-García M, Crespo-Ramírez M, Flores-Gracia C et al. Anxiolytic-like effects of the selective metabotropic glutamate receptor 5 antagonist MPEP after its intra-amygdaloid microinjection in three different non-conditioned rat models of anxiety. Eur J Neurosci 2006; 23: 2749–2759.
Page G, Khidir F, Pain S, Barrier L, Fauconneau B, Guillard O et al. Group I metabotropic glutamate receptors activate the p70S6 kinase via both mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK 1/2) signaling pathways in rat striatal and hippocampal synaptoneurosomes. Neurochem Int 2006; 49: 413–421.
Hou L, Klann E . Activation of the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin signaling pathway is required for metabotropic glutamate receptor-dependent long-term depression. J Neurosci 2004; 24: 6352–6361.
Breier A, Malhotra A, Pinals D, Weisenfeld N, Pickar D . Association of ketamine-induced psychosis with focal activation of the prefrontal cortex in healthy volunteers. Am J Psychiatry 1997; 154: 805–811.
Vollenweider F, Leenders K, Scharfetter C, Antonini A, Maguire P, Missimer J et al. Metabolic hyperfrontality and psychopathology in the ketamine model of psychosis using positron emission tomography (PET) and [18F]fluorodeoxyglucose(FDG). Eur Neuropsychopharmacol 1997; 7: 9–24.
Rowland L, Beason-Held L, Tamminga C, Holcomb H . The interactive effects of ketamine and nicotine on human cerebral blood flow. Psychopharmacology 2010; 208: 575–584.
Akkus F, Ametamey S, Treyer V, Burger C, Johayem A, Umbricht D et al. Marked global reduction in mGluR5 receptor binding in smokers and ex-smokers determined by [11C]ABP688 positron emission tomography. Proc Natl Acad Sci USA 2013; 110: 334.
Acknowledgements
We thank Ms Samantha Rossano for her contributions to the data analysis and manuscript development. We also thank the Yale University Positron Emission Tomography Center staff for their aid with radiotracer syntheses, related analyses and subject imaging. We acknowledge the biostatistical consultation and support from the Biostatistical Consulting Core at the School of Medicine, Stony Brook University. Support was provided by K01MH092681 (to IE), VA National Center for PTSD (to IE, JHK, RHP, CGA), K01MH091354 (to CD) and R01MH104512 (to CD).
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JHK: (1) Vladimir, Coric, Krystal, John H, Sanacora, Gerard—Glutamate Modulating Agents in the Treatment of Mental Disorders US Patent No. 8,778,979 B2 Patent Issue Date: 15 July 2014. (2) Charney D, Krystal JH, Manji H, Matthew S, Zarate C—Intranasal Administration of Ketamine to Treat Depression United States Application No. 14/197,767 filed on 5 March 2014; United States application or PCT International application No. 14/306,382 filed on 17 June 2014. He was also on consultant/advisory board for: AMGEN, AstraZeneca Pharmaceuticals, Biogen, Idec, MA, Biomedisyn Corporation, Forum Pharmaceuticals, Janssen Research & Development, Otsuka America Pharmaceutical, Inc., Sunovion Pharmaceuticals, Inc., Takeda Industries, Taisho Pharmaceutical Co., Ltd, Biohaven Pharmaceuticals, Blackthorn Therapeutics, Inc., Lohocla Research Corporation, Luc Therapeutics, Inc., Pfizer Pharmaceuticals, and TRImaran Pharma. GS has received consulting fees form Allergan, Alkermes, AstraZeneca, BioHaven Pharmaceuticals, Hoffman La-Roche, Janssen, Merck, Naurex, Servier Pharmaceuticals, Taisho Pharmaceuticals, Teva, Valenant pharmaceutical North America and Vistagen therapeutics over the past 24 months. He has also received additional research contracts from AstraZeneca, Bristol-Myers Squibb, Eli Lilly & Co., Johnson & Johnson, Hoffman La-Roche, Merck & Co., Naurex and Servier over the past 24 months. Free medication was provided to GS for an NIH sponsored study by Sanofi-Aventis. In addition, he holds shares in BioHaven Pharmaceuticals Holding Company and is a co-inventor on a patent ‘Glutamate agents in the treatment of mental disorders’ Patent number: 8778979. RHP: Scientific Consultant to Cogstate, Ltd. CGA served on advisory boards for Genentech. REC received research support from Astra-Zeneca, Astellas, BMS, Pfizer, Siemens, Taisho and UCB. The other authors declare no conflict of interest.
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Esterlis, I., DellaGioia, N., Pietrzak, R. et al. Ketamine-induced reduction in mGluR5 availability is associated with an antidepressant response: an [11C]ABP688 and PET imaging study in depression. Mol Psychiatry 23, 824–832 (2018). https://doi.org/10.1038/mp.2017.58
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DOI: https://doi.org/10.1038/mp.2017.58
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