title: Imaging glutamate homeostasis in cocaine addiction with the metabotropic glutamate receptor 5 positron emission tomography radiotracer [(11)C]ABP688 and magnetic resonance spectroscopy.
abstract: BACKGROUND
  Preclinical studies demonstrate that glutamate homeostasis in the striatum is disrupted following cocaine exposure, including a decrease in metabotropic glutamate receptor type 5 (mGluR5) expression and reduced glutamate turnover. The goal of this study was to use imaging of the human brain to investigate alterations in the glutamate signaling in cocaine addiction.
  
  
  METHODS
  Positron emission tomography imaging with the radiotracer [(11)C]ABP688 was used to measure mGluR5 binding and magnetic resonance spectroscopy was used to measure glutamate-glutamine levels in the striatum of cocaine-addicted participants (n = 15) compared with healthy control subjects (n = 15). Following the scans, the cocaine-addicted volunteers performed cocaine self-administration sessions to investigate the correlation between cocaine-seeking behavior and mGluR5 receptor binding.
  
  
  RESULTS
  The results of the study showed that cocaine addiction was associated with a 20% to 22% reduction in [(11)C]ABP688 binding in the striatum. A secondary analysis of cortical and subcortical regions other than the striatum showed a similar reduction in [(11)C]ABP688 binding, suggesting that the decrease was widespread. No between-group differences were seen in the magnetic resonance spectroscopy measures of glutamate-glutamine in the left striatum. In addition, no correlation was seen between [(11)C]ABP688 binding in the striatum and the choice to self-administer cocaine.
  
  
  CONCLUSIONS
  Overall, these results show that long-term cocaine use is associated with a decrease in mGluR5 availability compared with matched healthy control subjects and suggests that this receptor may serve as a viable target for treatment development for this disorder.
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York, New York. Electronic address: dm437@columbia.edu.
authors.forename: Diana
authors.initials: D
authors.lastname: Martinez
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York, New York.
authors.forename: Mark
authors.initials: M
authors.lastname: Slifstein
authors.affiliation: Department of Psychiatry, Yale Positron Emission Tomography Center, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Nabeel
authors.initials: N
authors.lastname: Nabulsi
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York, New York.
authors.forename: Alexander
authors.initials: A
authors.lastname: Grassetti
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York, New York.
authors.forename: Nina B L
authors.initials: NB
authors.lastname: Urban
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York, New York.
authors.forename: Audrey
authors.initials: A
authors.lastname: Perez
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York, New York.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Psychiatry, Yale Positron Emission Tomography Center, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Shu-Fei
authors.initials: SF
authors.lastname: Lin
authors.affiliation: Department of Psychiatry, Yale Positron Emission Tomography Center, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Jim
authors.initials: J
authors.lastname: Ropchan
authors.affiliation: Department of Radiology, Weill Medical College of Cornell University, New York, New York.
authors.forename: Xiangling
authors.initials: X
authors.lastname: Mao
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York, New York.
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Kegeles
authors.affiliation: Department of Radiology, Weill Medical College of Cornell University, New York, New York.
authors.forename: Dikoma C
authors.initials: DC
authors.lastname: Shungu
authors.affiliation: Department of Psychiatry, Yale Positron Emission Tomography Center, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
authors.affiliation: Department of Psychiatry, Yale Positron Emission Tomography Center, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002250:Carbon Radioisotopes; D016022:Case-Control Studies; D002755:Choice Behavior / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage; D019970:Cocaine-Related Disorders / Q000000981:diagnostic imaging / Q000378:metabolism*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D059907:Functional Neuroimaging; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010091:Oximes; D049268:Positron-Emission Tomography; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism*; D012646:Self Administration; D055815:Young Adult
chemical_list: C510950:3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime; D002250:Carbon Radioisotopes; D010091:Oximes; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D005973:Glutamine; D018698:Glutamic Acid; D003042:Cocaine
keywords: Addiction; cocaine; cocaine self-administration; magnetic resonance spectroscopy; metabotropic glutamate receptor 5; positron emission tomography
references.citation: Am J Psychiatry. 2000 Jul;157(7):1134-40
references.pmid: 10873923
references.citation: J Neurosci. 2010 Jun 9;30(23):7984-92
references.pmid: 20534846
references.citation: Neuropsychopharmacology. 2004 Jun;29(6):1190-202
references.pmid: 15010698
references.citation: Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5662-6
references.pmid: 8516315
references.citation: Eur J Pharmacol. 2004 Sep 19;499(1-2):121-33
references.pmid: 15363959
references.citation: Drug Alcohol Depend. 2010 Sep 1;111(1-2):97-104
references.pmid: 20537812
references.citation: Neuroscience. 2003;117(2):461-75
references.pmid: 12614686
references.citation: Neuropsychopharmacology. 2012 Aug;37(9):2143-52
references.pmid: 22549117
references.citation: Synapse. 2001 Sep 15;41(4):275-84
references.pmid: 11494398
references.citation: Brain Res Bull. 2009 May 29;79(3-4):215-8
references.pmid: 19166917
references.citation: Neurosci Lett. 2009 Mar 13;452(2):167-71
references.pmid: 19118598
references.citation: Arch Gen Psychiatry. 2012 May;69(5):449-59
references.pmid: 22213769
references.citation: Psychopharmacology (Berl). 2010 Aug;211(3):267-75
references.pmid: 20544343
references.citation: J Neurophysiol. 2005 Apr;93(4):1989-2001
references.pmid: 15590730
references.citation: J Neurosci. 2003 Apr 15;23(8):3531-7
references.pmid: 12716962
references.citation: Nucl Med Biol. 2007 Nov;34(8):1009-17
references.pmid: 17998106
references.citation: Neuropsychopharmacology. 2006 Apr;31(4):778-86
references.pmid: 16123768
references.citation: Psychiatry Res. 2009 Dec 30;174(3):171-6
references.pmid: 19906515
references.citation: J Cereb Blood Flow Metab. 2011 Nov;31(11):2169-80
references.pmid: 21792244
references.citation: Psychopharmacology (Berl). 2011 Oct;217(3):367-75
references.pmid: 21494788
references.citation: Biol Psychiatry. 2011 May 1;69(9):822-4
references.pmid: 21288506
references.citation: Mol Psychiatry. 2014 May;19(5):625-32
references.pmid: 23628984
references.citation: Synapse. 2009 Jul;63(7):598-609
references.pmid: 19306440
references.citation: Am J Psychiatry. 2004 Jul;161(7):1211-8
references.pmid: 15229053
references.citation: J Nucl Med. 2007 Feb;48(2):247-52
references.pmid: 17268022
references.citation: Psychopharmacology (Berl). 2008 Feb;196(2):303-13
references.pmid: 17940751
references.citation: Psychopharmacology (Berl). 2005 Apr;179(1):247-54
references.pmid: 15602687
references.citation: Proc Natl Acad Sci U S A. 2013 Jan 8;110(2):737-42
references.pmid: 23248277
references.citation: Biol Psychiatry. 2009 Apr 15;65(8):717-20
references.pmid: 19100966
references.citation: Addiction. 2012 Jan;107(1):131-41
references.pmid: 21707811
references.citation: J Cereb Blood Flow Metab. 2010 Aug;30(8):1538-49
references.pmid: 20531460
references.citation: J Pharmacol Exp Ther. 2005 Mar;312(3):1232-40
references.pmid: 15550570
references.citation: Eur J Pharmacol. 2008 Aug 20;590(1-3):157-62
references.pmid: 18598691
references.citation: Am J Psychiatry. 2007 Apr;164(4):622-9
references.pmid: 17403976
references.citation: Biol Psychiatry. 2010 Aug 1;68(3):240-8
references.pmid: 20416862
references.citation: J Cereb Blood Flow Metab. 2003 Mar;23(3):285-300
references.pmid: 12621304
references.citation: Behav Brain Res. 2009 Sep 14;202(2):238-44
references.pmid: 19463707
references.citation: Proc Natl Acad Sci U S A. 2011 Jan 4;108(1):385-90
references.pmid: 21173236
references.citation: Psychopharmacology (Berl). 2005 Apr;179(1):255-61
references.pmid: 15619120
references.citation: Behav Neurosci. 2011 Feb;125(1):10-9
references.pmid: 21319882
references.citation: Am J Psychiatry. 2011 Jun;168(6):634-41
references.pmid: 21406463
references.citation: J Cereb Blood Flow Metab. 2000 Feb;20(2):225-43
references.pmid: 10698059
references.citation: Synapse. 2003 Mar;47(3):240-2
references.pmid: 12494407
references.citation: Eur J Nucl Med Mol Imaging. 2011 Jun;38(6):1083-94
references.pmid: 21279350
references.citation: Neuroimage. 1997 Nov;6(4):279-87
references.pmid: 9417971
references.citation: Am J Psychiatry. 2011 Jul;168(7):727-34
references.pmid: 21498461
references.citation: Psychopharmacology (Berl). 2008 Oct;200(2):167-76
references.pmid: 18509621