1. Striatal changes underlie MPEP-mediated suppression of the acquisition and expression of pramipexole-induced place preference in an alpha-synuclein rat model of Parkinson's disease.
- Author
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Loiodice, Simon, Mcghan, Portia, Gryshkova, Vitalina, Fleurance, Renaud, Dardou, David, Hafidi, Aziz, Nogueira, Da Costa Andre, Durif, Franck, and Nogueira Da Costa, Andre
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DRUG therapy for Parkinson's disease ,PRAMIPEXOLE ,ALPHA-synuclein ,NUCLEUS accumbens ,TARDIVE dyskinesia ,DIAGNOSIS ,THERAPEUTICS - Abstract
Impulsive-compulsive disorders in Parkinson's disease patients have been described as behavioural or substance addictions including pathological gambling or compulsive medication use of dopamine replacement therapy. A substantial gap remains in the understanding of these disorders. We previously demonstrated that the rewarding effect of the D2/D3 agonist pramipexole was enhanced after repeated exposure to L-dopa and alpha-synuclein mediated dopaminergic nigral loss with specific transcriptional signatures suggesting a key involvement of the glutamatergic pathway. Here, we further investigate the therapeutic potential of metabotropic glutamate receptor 5 antagonism in Parkinson's disease/dopamine replacement therapy related bias of reward-mediated associative learning. We identified protein changes underlying the striatal remodelling associated with the pramipexole-induced conditioned place preference. Acquisition and expression of the pramipexole-induced conditioned place preference were abolished by the metabotropic glutamate receptor 5 antagonist 2-methyl-6-phenylethynyl (pyridine) (conditioned place preference scores obtained with pramipexole conditioning were reduced by 12.5% and 125.8% when 2-methyl-6-phenylethynyl (pyridine) was co-administrated with pramipexole or after the pramipexole conditioning, respectively). Up-regulation of the metabotropic glutamate receptor 5 was found in the dorsomedial-striatum and nucleus accumbens core. Activation of these two brain sub-regions was also highlighted through FosB immunohistochemistry. Convergent molecular and pharmacological data further suggests metabotropic glutamate receptor 5 as a promising therapeutic target for the management of Parkinson's disease/dopamine replacement therapy related reward bias. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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