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 [ 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.