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An influence of ligands of metabotropic glutamate receptor subtypes on parkinsonian-like symptoms and the striatopallidal pathway in rats

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Summary.

Several data indicate that inhibition of glutamatergic transmission may be important to alleviate of parkinsonian symptoms. Therefore, the aim of the present paper is to review recent studies on the search for putative antiparkinsonian-like effects of mGluR ligands and their brain targets. In order to inhibit glutamatergic transmission, the group I mGluRs (mGluR1 and mGluR5) were blocked, and group II (mGluR2/3) or III (mGluR4/7/8) mGluRs were activated.

Systemic or intrastriatal administration of group I mGluR antagonists (mGluR5 – MPEP, MTEP; mGluR1 – AIDA) was found to inhibit parkinsonian-like symptoms (catalepsy, muscle rigidity) in rats. MPEP administered systemically and mGluR1 antagonists (AIDA, CPCCOEt, LY367385) injected intrastriatally reversed also the haloperidol-increased proenkephalin (PENK) mRNA expression in the striatopallidal pathway. Similarly, ACPT-1, a group III mGluR agonist, administered into the striatum, globus pallidus or substantia nigra inhibited the catalepsy. Intrastriatal injection of this compound reduced the striatal PENK expression induced by haloperidol. In contrast, a group II mGluR agonist (2R,4R-APDC) administered intrastriatally reduced neither PENK expression nor the above-mentioned parkinsonian-like symptoms. Moreover, a mixed mGluR8 agonist/AMPA antagonist, (R,S)-3,4-DCPG, administered systemically evoked catalepsy and enhanced both the catalepsy and PENK expression induced by haloperidol.

The results reviewed in this article seem to indicate that group I mGluR antagonists or some agonists of group III may possess antiparkinsonian properties, and point at the striatopallidal pathway as a potential target of therapeutic intervention.

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Authors and Affiliations

  1. Department of Neuro-Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland

    K. Ossowska, J. Konieczny, J. Wardas, M. Pietraszek, K. Kuter & S. Wolfarth

  2. Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland

    A. Pilc

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  1. K. Ossowska
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  2. J. Konieczny
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  3. J. Wardas
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  4. M. Pietraszek
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  7. A. Pilc
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Ossowska, K., Konieczny, J., Wardas, J. et al. An influence of ligands of metabotropic glutamate receptor subtypes on parkinsonian-like symptoms and the striatopallidal pathway in rats. Amino Acids 32, 179–188 (2007). https://doi.org/10.1007/s00726-006-0317-y

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