title: Imaging in vivo glutamate fluctuations with [(11)C]ABP688: a GLT-1 challenge with ceftriaxone.
abstract: 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.
authors: 1] Translational Neuroimaging Laboratory (TNL), McGill Center for Studies in Aging, Douglas Mental Health University Institute, Verdun, Quebec, Canada [2] Alzheimer's Disease Research Unit, McGill Centre for Studies in Aging, McGill University, Montreal, Quebec, Canada [3] Department of Biochemistry, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors: Eduardo R
authors: ER
authors: Zimmer
authors: 1] Translational Neuroimaging Laboratory (TNL), McGill Center for Studies in Aging, Douglas Mental Health University Institute, Verdun, Quebec, Canada [2] Alzheimer's Disease Research Unit, McGill Centre for Studies in Aging, McGill University, Montreal, Quebec, Canada.
authors: Maxime J
authors: MJ
authors: Parent
authors: 1] Translational Neuroimaging Laboratory (TNL), McGill Center for Studies in Aging, Douglas Mental Health University Institute, Verdun, Quebec, Canada [2] Alzheimer's Disease Research Unit, McGill Centre for Studies in Aging, McGill University, Montreal, Quebec, Canada.
authors: Antoine
authors: A
authors: Leuzy
authors: Montreal Neurological Institute (MNI), Montreal, Quebec, Canada.
authors: Antonio
authors: A
authors: Aliaga
authors: Translational Neuroimaging Laboratory (TNL), McGill Center for Studies in Aging, Douglas Mental Health University Institute, Verdun, Quebec, Canada.
authors: Arturo
authors: A
authors: Aliaga
authors: Department of Psychiatry, Douglas Hospital Research Centre, McGill University, Montreal, Quebec, Canada.
authors: Luc
authors: L
authors: Moquin
authors: Montreal Neurological Institute (MNI), Montreal, Quebec, Canada.
authors: Esther S
authors: ES
authors: Schirrmacher
authors: Montreal Neurological Institute (MNI), Montreal, Quebec, Canada.
authors: Jean-Paul
authors: JP
authors: Soucy
authors: Montreal Neurological Institute (MNI), Montreal, Quebec, Canada.
authors: Ivan
authors: I
authors: Skelin
authors: Department of Psychiatry, Douglas Hospital Research Centre, McGill University, Montreal, Quebec, Canada.
authors: Alain
authors: A
authors: Gratton
authors: Alzheimer's Disease Research Unit, McGill Centre for Studies in Aging, McGill University, Montreal, Quebec, Canada.
authors: Serge
authors: S
authors: Gauthier
authors: 1] Translational Neuroimaging Laboratory (TNL), McGill Center for Studies in Aging, Douglas Mental Health University Institute, Verdun, Quebec, Canada [2] Alzheimer's Disease Research Unit, McGill Centre for Studies in Aging, McGill University, Montreal, Quebec, Canada [3] Montreal Neurological Institute (MNI), Montreal, Quebec, Canada.
authors: Pedro
authors: P
authors: Rosa-Neto
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes / Q000378:metabolism*; D002443:Ceftriaxone / Q000494:pharmacology*; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism*; D018698:Glutamic Acid / Q000032:analysis / Q000378:metabolism*; D010091:Oximes / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism; D013788:Thalamus / Q000378:metabolism*
chemical_list: C510950:3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime; D002250:Carbon Radioisotopes; D027342:Excitatory Amino Acid Transporter 2; D010091:Oximes; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018698:Glutamic Acid; D002443:Ceftriaxone