Imaging glutamate homeostasis in cocaine addiction with the metabotropic glutamate receptor 5 positron emission tomography radiotracer [(11)C]ABP688 and magnetic resonance spectroscopy.
| Publication Type | Academic Article |
| Authors | Martinez D, Slifstein M, Nabulsi N, Grassetti A, Urban N, Perez A, Liu F, Lin S, Ropchan J, Mao X, Kegeles L, Shungu D, Carson R, Huang Y |
| Journal | Biol Psychiatry |
| Volume | 75 |
| Issue | 2 |
| Pagination | 165-71 |
| Date Published | 09/12/2013 |
| ISSN | 1873-2402 |
| Keywords | Cocaine-Related Disorders, Corpus Striatum, Glutamic Acid, Glutamine, Homeostasis, Oximes, Pyridines, Receptor, Metabotropic Glutamate 5 |
| 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. |
| DOI | 10.1016/j.biopsych.2013.06.026 |
| PubMed ID | 24035345 |
| PubMed Central ID | PMC4106018 |