Characterizing the modulation of mGluR5 in a 6-OHDA-induced rat model of Parkinson's disease

Abstract

MicroPET imaging studies were conducted to investigate the role of metabotropic glutamate subtype-5 receptors (mGluR5) in Parkinson's disease (PD). Four analogical PET ligands were used to characterize modulation of mGluR5 function in a 6hydroxydopamine (6-OHDA) induced rat model of PD. Unilateral 6-OHDA lesions were made in the right medial forebrain bundle, and severity of these lesions was determined with [¹¹]CFT. The binding characteristics of the PET ligands were analyzed using a modified distribution volume method of the Logan reference region model. Binding potential values were calculated on the striatum, hippocampus, and cortex, using the cerebellum as a reference tissue. On the right (with lesion) side of the striatum, ["C]CFT binding decreased. Three of the four investigated mGluR5 ligands ([¹¹C]MPEP, [¹¹C]M-PEPy, and [¹¹C]MMPEP) also showed enhanced binding characteristics on the same side of the brain. The right hippocampus and cortex showed similar results. The mGluR5s' enhanced binding characteristics on the right side of the brain suggest a complementary and compensatory role of metabotropic glutamate receptors in the dopaminergic neurodegeneration of Parkinson's disease.