Objective: To determine the distribution and density of metabotropic glutamate 2 (mGlu₂) receptors in the motor loop of the basal ganglia in 6-hydroxydopamine (6-OHDA)-lesioned rats with L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia.

Background: L-DOPA-induced dyskinesia affects nearly 90% of Parkinson’s disease patients after long-term treatment with L-DOPA. Previous studies have shown that mGlu₂ activation alleviates dyskinesia in the parkinsonian rat and marmoset. Further insight into the distribution of mGlu₂ receptors in brain areas implicated in mediating such anti-dyskinetic effects is needed.

Method: Rats were rendered parkinsonian by 6-OHDA injection. Parkinsonism was determined using the cylinder test and dyskinesia severity was assessed with the abnormal involuntary movements (AIMs) scale. Brain sections were selected from 4 different groups: dyskinetic and non-dyskinetic L-DOPA-treated 6-OHDA rats, L-DOPA-naïve 6-OHDA rats, and sham-lesioned rats. MGlu₂ receptors were measured in the motor cortex (M1), striatum, globus pallidus (GP), entopeduncular nucleus (EP), subthalamic nucleus (STN), substantia nigra (SN), and ventral lateral (VL) nucleus of the thalamus by autoradiographic binding with the radioligand [³H]-LY-341,495 and L-glutamic acid as the cold ligand.

Results: In the ipsilateral hemisphere, non-dyskinetic rats exhibited a decrease in [³H]-LY-341,495 binding in the GP (28% vs sham-lesioned, P < 0.05; 23% vs L-DOPA-naïve, P < 0.001), and a decrease in M1 (49% vs sham-lesioned, P < 0.05; 45% vs L-DOPA-naïve, P < 0.001). Dyskinetic rats showed an increase in binding in M1 (43% vs non-dyskinetic, P < 0.05). In the contralateral hemisphere, non-dyskinetic rats showed a decrease in binding in the EP (30% vs sham-lesioned; 24% vs L-DOPA-naïve, both P < 0.05), a decrease in the GP (34% vs sham-lesioned, P < 0.05; 23% vs L-DOPA-naïve, P < 0.001), and a decrease in M1 (50% vs sham-lesioned; 44% vs L-DOPA-naïve, both P < 0.05). Dyskinetic rats showed a decrease in binding in the GP (30% vs sham-lesioned; 19% vs L-DOPA-naïve, both P < 0.05).

Conclusion: The results indicate L-DOPA treatment may be altering mGlu₂ expression in specific brain regions, suggesting that mGlu₂ receptors are part of a compensatory mechanism against dyskinesia.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/determination-of-metabotropic-glutamate-2-receptor-distribution-with-3h-ly-341495-in-hemi-parkinsonian-rats-with-l-dopa-induced-dyskinesia/