HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

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

AbstractBACKGROUND:
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.
AuthorsDiana Martinez, Mark Slifstein, Nabeel Nabulsi, Alexander Grassetti, Nina B L Urban, Audrey Perez, Fei Liu, Shu-Fei Lin, Jim Ropchan, Xiangling Mao, Lawrence S Kegeles, Dikoma C Shungu, Richard E Carson, Yiyun Huang
JournalBiological psychiatry (Biol Psychiatry) Vol. 75 Issue 2 Pg. 165-71 (Jan 15 2014) ISSN: 1873-2402 [Electronic] United States
PMID24035345 (Publication Type: Journal Article, Observational Study, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Chemical References
  • 3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime
  • Carbon Radioisotopes
  • Oximes
  • Pyridines
  • Receptor, Metabotropic Glutamate 5
  • Glutamine
  • Glutamic Acid
  • Cocaine
Topics
  • Adult
  • Brain (diagnostic imaging, metabolism)
  • Carbon Radioisotopes
  • Case-Control Studies
  • Choice Behavior (drug effects)
  • Cocaine (administration & dosage)
  • Cocaine-Related Disorders (diagnostic imaging, metabolism)
  • Corpus Striatum (diagnostic imaging, 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

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: