A.C.V. and S.P. contributed equally to this work.
Neuroprotective effects of metabotropic glutamate receptor ligands in a 6-hydroxydopamine rodent model of Parkinson's disease
Article first published online: 3 OCT 2005
European Journal of Neuroscience
Volume 22, Issue 7, pages 1799–1806, October 2005
How to Cite
Vernon, A. C., Palmer, S., Datla, K. P., Zbarsky, V., Croucher, M. J. and Dexter, D. T. (2005), Neuroprotective effects of metabotropic glutamate receptor ligands in a 6-hydroxydopamine rodent model of Parkinson's disease. European Journal of Neuroscience, 22: 1799–1806. doi: 10.1111/j.1460-9568.2005.04362.x
- Issue published online: 3 OCT 2005
- Article first published online: 3 OCT 2005
- Received 9 August 2004, revised 2 August 2005, accepted 4 August 2005
- metabotropic glutamate receptors;
- Parkinson's disease
Increasing evidence implicates glutamate-mediated excitotoxicity as a contributory factor in dopaminergic cell death in the substantia nigra 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 striatal dopamine (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)-(+)-α-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 of mGluR ligands in vivo against 6-OHDA toxicity that has important implications for the treatment of PD.