Premium
Neuroprotective effects of metabotropic glutamate receptor ligands in a 6‐hydroxydopamine rodent model of Parkinson's disease
Author(s) -
Ver A. C.,
Palmer S.,
Datla K. P.,
Zbarsky V.,
Croucher M. J.,
Dexter D. T.
Publication year - 2005
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2005.04362.x
Subject(s) - hydroxydopamine , neuroprotection , parkinson's disease , neuroscience , metabotropic glutamate receptor , metabotropic glutamate receptor 5 , glutamate receptor , medicine , pharmacology , psychology , disease , receptor
Abstract 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 (2 R ,4 R )‐4‐aminopyrrolidine‐2,4‐dicarboxylate ( 2 R ,4 R ‐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.