Imaging Glutamate Homeostasis in Cocaine Addiction with the Metabotropic Glutamate Receptor 5 Positron Emission Tomography Radiotracer [11C]ABP688 and Magnetic Resonance Spectroscopy

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 [C-11]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 [C-11]ABP688 binding in the striatum. A secondary analysis of cortical and subcortical regions other than the striatum showed a similar reduction in [C-11]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 [C-11]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.