Recent technical development of different imaging modalities has enabled exploration of basic biological functions and their regulatory mechanisms in living objects. In vivo imaging is important because many regulatory mechanisms are time dependent and have inhibitory or excitatory properties in the physiological processes. Glutamate is the most abundantly active neurotransmitter in the mammalian brain and mediates the excitatory pathways in mammals. There is considerable experimental evidence that metabotropic excitatory amino acid (EAA) receptors are involved in the regulation of synaptic transmission in the cerebronervous system (CNS). However, the lack of specific agonists and antagonists has limited the precise characterization of the role of individual metabotropic glutamate receptors in glutamatergic neurotransmission and has hampered progress in identifying the physiological and pathological roles of mGluRs. We are proposing to develop precursors and radiolabeling techniques for several different ligands, which are specific antagonists for mGluR5 (subgroup I) or mGluR2/3 (subgroup II), respectively. After determination of the bioavailability and pharmacokinetics of these ligands in experimental rodent studies, the most selective and sensitive ligands will be selected. These radiolabeled ligands will be used to evaluate mGluR5 and mGluR2/3 receptor function with positron emission tomography techniques in normal primate brain and in a primate Parkinson's disease model as an endpoint aim to explore a role of mGluR5 and mGluR2/3 receptors in glutamatergic neurotransmission and a possible link between glutamatergic and dopaminergic receptor function in progressive neurodegeneration.
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