SHORT COMMUNICATION Neuroprotective effects of metabotropic glutamate receptor ligands in a 6-hydroxydopamine rodent model of Parkinson's disease

Abstract Increasing evidence implicates glutamate-mediated excitotoxicity as a contributory factor in dopaminergic cell death in the substantianigra pars compacta (SNc) in Parkinson’s disease (PD). Previous studies have suggested that metabotropic glutamate receptor(mGluR) ligands are neuroprotective against excitotoxicity in vitro. In the present study, the neurotoxin 6-hydroxydopamine (6-OHDA)produced a significant loss (61.2 ± 8.9%; P < 0.01) of tyrosine hydroxylase-immunopositive (TH+) cells in both the SNc and striataldopamine (58.02 ± 1.27%; P < 0.05) in control male Sprague–Dawley rats. Both losses were significantly attenuated by sub-chronic(7 day) treatment with the Group I mGluR antagonists, 2-methyl-6(phenylethynyl)-pyridine (MPEP) or (S)-(+)-a-amino-4-carboxy-2-methylbenzeneacetic acid (LY367385); the Group II mGluR agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC);or the Group III mGluR agonist, l (+)-2-amino-4-phosphonobutyric acid (L-AP4). These data demonstrate a neuroprotective action ofmGluR ligands in vivo against 6-OHDA toxicity that has important implications for the treatment of PD.

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