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Biol Psychiatry. 2014 Jan 15;75(2):165-71. doi: 10.1016/j.biopsych.2013.06.026. Epub 2013 Sep 12.

Imaging glutamate homeostasis in cocaine addiction with the metabotropic glutamate receptor 5 positron emission tomography radiotracer [(11)C]ABP688 and magnetic resonance spectroscopy.

Author information

  • 1Department 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.
  • 2Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York, New York.
  • 3Department of Psychiatry, Yale Positron Emission Tomography Center, Yale University School of Medicine, New Haven, Connecticut.
  • 4Department of Radiology, Weill Medical College of Cornell University, New York, New York.

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.

Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

KEYWORDS:

Addiction; cocaine; cocaine self-administration; magnetic resonance spectroscopy; metabotropic glutamate receptor 5; positron emission tomography

PMID:
24035345
[PubMed - indexed for MEDLINE]
PMCID:
PMC4106018
Free PMC Article
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