Glutamatergic biomarkers for cocaine addiction: a longitudinal study using MRS and GluR5 PET in self-administering rats

Cocaine addiction is a disorder that still lacks diagnostic biomarkers or effective pharmacotherapy. We present findings in a rat model of cocaine self-administration that was followed-up longitudinally using the metabotropic glutamate receptor 5 (mGluR5) tracer 18F-FPEB positron emission tomography (PET), proton magnetic resonance spectroscopy (1H-MRS) and behavioral tests. Methods: Forty-two Wistar rats were scanned with 18F-FPEB PET and 1H-MRS before and after sucrose or IV cocaine self-administration, during withdrawal and relapse. All animals performed a rodent Iowa Gambling Task (rIGT) at baseline to evaluate decision-making. Baseline values were used in a mixed model to assess associations with later cocaine use and follow-up measurements were compared to the values before drug exposure. Results: Pre-exposure rIGT scores were significantly related to both cocaine and sucrose use during the drug-exposure phase. However, only cocaine self-administration induced a decrease in 18F-FPEB binding. This decrease was most pronounced in the bilateral hippocampus, where mGluR5 availability correlated with the amount of cocaine used during relapse. Compared to the sucrose group, a larger decrease was observed in the hippocampo-prefrontal cortex pathway. Pre-exposure glutamate and glycine concentrations in the prefrontal cortex were significantly associated with cocaine use during the drug-exposure phase. Moreover, prefrontal glutamate exhibited a distinct, reversible decrease when animals had access to cocaine, but not sucrose. Conclusion: Baseline values of prefrontal glutamate and glycine are associated with future cocaine use. Furthermore, baseline rIGT scores are associated with both sucrose and cocaine. Finally, we found that both glutamate concentration and mGluR5 availability decrease during exposure to cocaine.

Publication year:2018

BOF-keylabel:yes

IOF-keylabel:yes

BOF-publication weight:10

CSS-citation score:1

Authors from:Higher Education

Accessibility:Open