Pharmacological stimulation of metabotropic glutamate receptor type 4 in a rat model of Parkinson's disease and L-DOPA-induced dyskinesia: Comparison between a positive allosteric modulator and an orthosteric agonist

Neuropharmacology
Hanna IderbergM Angela Cenci

Abstract

Metabotropic glutamate receptor 4 (mGlu4) negatively modulates GABA and glutamate release in the 'indirect pathway' of the basal ganglia, and has thus been proposed as a potential target to treat motor symptoms in Parkinson's disease. Here, we present an extensive comparison of the behavioural effects produced by the mGlu4 positive allosteric modulator (PAM), VU0364770, and the mGlu4 orthosteric agonist, LSP1-2111, in rats with unilateral 6-OHDA lesions. The compounds' activity was initially assessed in a test of haloperidol-induced catalepsy in intact rats, and effective doses were then evaluated in the hemiparkinsonian animal model. Neither of the two compounds modified the development of dyskinetic behaviours elicited by chronic treatment with full doses of l-DOPA. When given together with l-DOPA to rats with already established dyskinesias, neither VU0364770 nor LSP1-2111 modified the abnormal involuntary movement scores. VU0364770 potentiated, however, the motor stimulant effect of a subthreshold l-DOPA dose in certain behavioural tests, whereas LSP1-2111 lacked this ability. Taken together, these results indicate that a pharmacological stimulation of mGlu4 lacks intrinsic antidyskinetic activity, but may have DOPA-sparing...Continue Reading

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Citations

Mar 31, 2016·Neuroscience and Biobehavioral Reviews·Tetsuya AsakawaYing Xia
Jul 26, 2015·Progress in Neurobiology·Matthieu F BastideErwan Bézard
Jul 28, 2017·Chinese Medical Journal·Juan-Juan Du, Sheng-Di Chen
Jun 21, 2017·Movement Disorders : Official Journal of the Movement Disorder Society·Tanya ChotibutMichael F Salvatore
Feb 2, 2018·Journal of Neural Transmission·Manuela Mellone, Fabrizio Gardoni
Nov 10, 2018·Expert Opinion on Pharmacotherapy·Nataša Dragašević-MiškovićVladimir S Kostić
Apr 12, 2019·Biomolecules·Fabio Del BelloWilma Quaglia
Apr 7, 2020·Journal of Parkinson's Disease·Elizabeth MannSusan Duty
Aug 14, 2020·CNS Drugs·Paulina Gonzalez-LatapiSusan H Fox
Sep 11, 2019·International Journal of Molecular Sciences·Zhu ZhangKen Kin-Lam Yung
Feb 26, 2019·Frontiers in Molecular Neuroscience·Rosalia CrupiSalvatore Cuzzocrea
Mar 27, 2018·Neuropharmacology·Delphine Charvin
Apr 6, 2021·The European Journal of Neuroscience·Isabelle WakuAmanda R de Oliveira
Aug 1, 2021·Neurotoxicology·Changqing Zheng, Feng Zhang

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