Imaging in vivo glutamate fluctuations with [(11)C]ABP688: a GLT-1 challenge with ceftriaxone.

TitleImaging in vivo glutamate fluctuations with [(11)C]ABP688: a GLT-1 challenge with ceftriaxone.
Publication TypeJournal Article
Year of Publication2015
AuthorsZimmer ER, Parent MJ, Leuzy A, Aliaga A, Aliaga A, Moquin L, Schirrmacher ES, Soucy J-P, Skelin I, Gratton A, Gauthier S, Rosa-Neto P
JournalJ Cereb Blood Flow Metab
Date Published2015 Jul
KeywordsAnimals, Carbon Radioisotopes, Ceftriaxone, Excitatory Amino Acid Transporter 2, Glutamic Acid, Oximes, Positron-Emission Tomography, Pyridines, Rats, Rats, Sprague-Dawley, Receptor, Metabotropic Glutamate 5, Thalamus

Molecular imaging offers unprecedented opportunities for investigating dynamic changes underlying neuropsychiatric conditions. Here, we evaluated whether [(11)C]ABP688, a positron emission tomography (PET) ligand that binds to the allosteric site of the metabotropic glutamate receptor type 5 (mGluR5), is sensitive to glutamate fluctuations after a pharmacological challenge. For this, we used ceftriaxone (CEF) administration in rats, an activator of the GLT-1 transporter (EAAT2), which is known to decrease extracellular levels of glutamate. MicroPET [(11)C]ABP688 dynamic acquisitions were conducted in rats after a venous injection of either saline (baseline) or CEF 200 mg/kg (challenge). Binding potentials (BP(ND)) were obtained using the simplified reference tissue method. Between-condition statistical parametric maps indicating brain regions showing the highest CEF effects guided placement of microdialysis probes for subsequent assessment of extracellular levels of glutamate. The CEF administration increased [(11)C]ABP688 BP(ND) in the thalamic ventral anterior (VA) nucleus bilaterally. Subsequent microdialysis assessment revealed declines in extracellular glutamate concentrations in the VA. The present results support the concept that availability of mGluR5 allosteric binding sites is sensitive to extracellular concentrations of glutamate. This interesting property of mGluR5 allosteric binding sites has potential applications for assessing the role of glutamate in the pathogenesis of neuropsychiatric conditions.

Alternate JournalJ. Cereb. Blood Flow Metab.
PubMed ID25806702
PubMed Central IDPMC4640271
Grant ListMOP-11-51-31 / / Canadian Institutes of Health Research / Canada