Effect of the metabotropic glutamate antagonist MPEP on striatal expression of the Homer family proteins in levodopa-treated hemiparkinsonian rats

Abstract

These results suggest that Homer protein family is not causally involved in the development of dyskinetic movements induced by levodopa treatment in this animal model of parkinsonism.

The metabotropic glutamate receptor antagonist 2‐methyl‐6‐(phenylethynyl) pyridine decreases striatal VGlut2 expression in association with an attenuation of L‐dopa‐induced dyskinesias

“…The administration of MPEP alone did not modify any of both markers. As previously shown, we found that the mGluR5 glutamate antagonist, MPEP reduced the dyskinetic movements elicited by levodopa treatment in 6‐OHDA‐lesioned rats and MPTP‐treated monkeys (Dekundy et al, 2006; Jiménez et al, 2009; Levandis et al, 2008; Mela et al, 2007; Morin et al, 2010). An attenuation of dyskinesias has also been observed in these models using other mGluR5 antagonists such as 3‐[(2‐methyl‐1,3‐thiazol‐4‐yl)ethynyl]pyridine (MTEP) (Gravius et al, 2008; Morin et al, 2010) In agreement with previous reports, we observed that striatal VGlut1 and VGlut2 were not different between intact and lesioned side in 6‐OHDA‐lesioned rats (Chung et al, 2006; Massie et al, 2010).…”

“…Brain glutamate overactivity is well documented in PD and antiglutamatergic drugs have been proposed to relieve PD symptoms and attenuate levodopa‐induced motor complications (Calon et al, 2003; Chase et al, 1996; Engber et al, 1994; Gubellini et al, 2006; Jiménez et al, 2009; Marin et al, 2000, 2001). It has been reported that metabotropic GluR5 specific binding is increased in the basal ganglia of parkinsonian monkeys that developed dyskinesias following chronic levodopa treatment (Samadi et al, 2008).…”

“…It has been reported that metabotropic GluR5 specific binding is increased in the basal ganglia of parkinsonian monkeys that developed dyskinesias following chronic levodopa treatment (Samadi et al, 2008). Over the past years, pharmacological antagonism of mGluR5 with the selective antagonists MPEP and MTEP was shown to inhibit expression of dyskinesias in the 6‐OHDA‐lesioned rat model of PD (Gravious et al, 2008; Jiménez et al, 2009; Levandis et al, 2008; Mela et al, 2007; Rylander et al, 2009; Yamamoto and Soghomonian, 2009) and MPTP monkeys (Morin et al, 2010).…”

“…The role of glutamate neurotransmission in the development and expression of LID is supported by the antidyskinetic activity of several glutamate receptor (GluR) antagonists in both, animal models of PD and clinical studies (Fox et al, 2006, Jiménez et al, 2009; Johnson et al, 2009, 2010). In this line, our group and others have been recently reported that antagonism of metabotropic GluR type 5 (mGluR5) attenuates the gradual development of LID in rats with 6‐hydroxydopamine (6‐OHDA) lesions (Jiménez et al, 2009; Mela et al, 2007) in association with a reduction in striatal levels of deltaFosB, a molecular marker causally related to LID (Jiménez et al, 2009). Pharmacological antagonism of mGluR5 can also inhibit the expression of dyskinesia in nonhuman primate models of PD (Hill et al, 2001; Johnston et al, 2010).…”

Increased efficacy of the 6-hydroxydopamine lesion of the median forebrain bundle in small rats, by modification of the stereotaxic coordinates

“…The use of double injection coordinates is a more recent phenomenon, often carried out in laboratories that have previously used single injection protocols, presumably in response to a similar drop off in lesion success to that seen in our laboratory (a conclusion supported by personal communications). The coordinates used by Jiménez et al (2009) are very close to those presented in the current work (allowing for the use of skull surface for the depth coordinate), including the use of a low nose-bar position.…”