The role of striatal metabotropic glutamate receptors in Parkinson's disease.

Abstract

The primary cause of Parkinson's disease is a loss of dopamine in the corpus striatum. It has been postulated that this effect leads to disinhibition of the striopallidal pathway and secondarily, to a functional shift towards glutamatergic stimulation. The aim of the present study was to find out whether inhibition of glutamatergic transmission at a level of metabotropic glutamate receptors (mGluRs) in the striatum may alleviate parkinsonian-like symptoms in rats. The non-competitive antagonist of receptor subtype 5 (mGluR5), MPEP (1.0-10 mg/kg ip), or the agonist of group II mGluRs, LY354,740 (5-10 mg/kg ip), reduced haloperidol-induced muscle rigidity and catalepsy. Intrastriatal injections of the mGluR1 antagonist, (RS) AIDA (7.5-15 microg/0.5 microl), but not of the agonist of group II mGluRs, 2R,4R-APDC (7.5-15 microg/0.5 microl), inhibited the muscle rigidity induced by haloperidol. In order to search for an influence of mGluRs on the striopallidal pathway, the effect of MPEP or of the agonist of group II mGluRs, DCG-IV, on the proenkephalin (PENK) mRNA expression in the dorso-lateral striatum was examined by an in situ hybridization. Repeated MPEP (6 x 10 mg/kg ip) administration did not influence PENK expression in naïve rats, but diminished that increased by haloperidol. In contrast, repeated DCG-IV (3 x 1 nmol/4 microl icv) injections enhanced both the control and the haloperidol-increased levels of PENK expression. The obtained results suggest that blockade of group I mGluRs, or stimulation of group II mGluRs may be important to ameliorate parkinsonian symptoms. Striatal mGluRs may contribute to at least some of these effects.

• Authors: K Ossowska, J Konieczny, J Wardas, K Gołembiowska, S Wolfarth, A Pilc
• Journal: Amino acids (Amino Acids) Vol. 23 Issue 1-3 Pg. 193-8 ( 2002) ISSN: 0939-4451 [Print] Austria
• PMID: 12373537 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antiparkinson Agents
• Enkephalins
• Excitatory Amino Acid Agonists
• Excitatory Amino Acid Antagonists
• Ligands
• Protein Isoforms
• Protein Precursors
• Receptors, Metabotropic Glutamate
• proenkephalin

Topics

• Animals
• Antiparkinson Agents (metabolism, therapeutic use)
• Corpus Striatum (cytology, metabolism)
• Enkephalins (metabolism)
• Excitatory Amino Acid Agonists (metabolism, therapeutic use)
• Excitatory Amino Acid Antagonists (metabolism, therapeutic use)
• Humans
• Ligands
• Parkinson Disease (drug therapy, metabolism)
• Protein Isoforms (metabolism)
• Protein Precursors (metabolism)
• Receptors, Metabotropic Glutamate (chemistry, metabolism)