Effect of the Metabotropic Glutamate Antagonist MPEP on Striatal Expression of the Homer Family Proteins in Levodopa-treated Hemiparkinsonian Rats

Rationale: Striatal glutamatergic hyperactivity through the metabotropic receptors and their intracellular signaling pathways is considered critical in the development of levodopa-induced dyskinesias in Parkinson's disease and in experimental parkinsonism.

Objective: We investigated whether the administration of the metabotropic glutamate antagonist, MPEP, modifies striatal expression of Homer family proteins which are involved in the intracellular mechanisms mediated by these receptors.

Materials And Methods: Sprague-Dawley rats were unilaterally lesioned in the nigrostriatal pathway with 6-hydroxydopamine (8 microg) and treated with: levodopa (12 mg/kg, i.p.) plus vehicle (n=10) divided in two daily injections; levodopa plus MPEP (1.5 and 3 mg/kg, i.p.; n=6-13) divided in two daily injections; or saline (n=7) for 10 consecutive days. Axial, limb, and orolingual dyskinesias were evaluated. Striatal expression of tyrosine hydroxylase (TH), Homer 1a, 1b/c, and deltaFosB were measured by Western Blot.

Results: Animals treated with levodopa showed an increase of dyskinesia score (p<0.01) that was attenuated by the administration of MPEP (p<0.01). In the ipsilateral side of the lesion, striatal TH expression was decreased (p<0.01). No significant differences in striatal Homer 1a or b/c expression were observed between the groups of treatment. Striatal deltaFosB expression increased in the animals treated with levodopa (p<0.05) being attenuated after MPEP administration (p<0.05). MPEP effect was not paralleled by any modification of striatal Homer proteins expression.

Conclusions: 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.