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

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


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.

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

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Carbon Radioisotopes
  • Case-Control Studies
  • Choice Behavior / drug effects
  • Cocaine / administration & dosage
  • Cocaine-Related Disorders / diagnostic imaging
  • Cocaine-Related Disorders / metabolism*
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / metabolism*
  • Functional Neuroimaging
  • Glutamic Acid / metabolism*
  • Glutamine / metabolism*
  • Homeostasis*
  • Humans
  • Magnetic Resonance Spectroscopy
  • Male
  • Oximes*
  • Positron-Emission Tomography
  • Pyridines*
  • Receptor, Metabotropic Glutamate 5 / metabolism*
  • Self Administration
  • Young Adult


  • 3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime
  • Carbon Radioisotopes
  • Oximes
  • Pyridines
  • Receptor, Metabotropic Glutamate 5
  • Glutamine
  • Glutamic Acid
  • Cocaine