RT Journal Article SR Electronic T1 Metabotropic Glutamate 5 Receptor Blockade Alleviates Akinesia by Normalizing Activity of Selective Basal-Ganglia Structures in Parkinsonian Rats JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 8302 OP 8309 DO 10.1523/JNEUROSCI.23-23-08302.2003 VO 23 IS 23 A1 Nathalie Breysse A1 Marianne Amalric A1 Pascal Salin YR 2003 UL http://www.jneurosci.org/content/23/23/8302.abstract AB Glutamate overactivity within the basal ganglia has been shown to be central to the expression of motor symptoms in advanced stages of Parkinson's disease, and metabotropic glutamate receptors (mGluRs) represent promising targets for new therapeutic strategies in this pathology. Little is known, however, about the cellular and behavioral changes occurring in the early stages of the disease when dopamine depletion is moderate. Here, we report that rats with partial bilateral dopamine lesions exhibit akinetic deficits associated with dramatically increased neuronal metabolic activity in selective structures of the basal ganglia such as the subthalamic nucleus and the substantia nigra pars reticulata, but not in the entopeduncular nucleus. Furthermore, chronic treatment with the mGluR5 antagonist 2-methyl-6-(phenylethylnyl)-pyridine alleviated the akinesia and was associated with a normalization of the activity of these two overactive structures. These data stress the therapeutic potential of mGluR5 antagonists in the treatment of parkinsonian patients in the early stages of the disease.