Objective: To determine the distribution and levels of metabotropic glutamate 2/3 (mGlu2/3) receptors in brain tissue from patients with Parkinson’s disease (PD) with visual hallucinations (VHs).

Background: VHs are one of the most common symptoms experienced by patients with advanced PD. Although the aetiology of VHs in PD remains unknown, previous studies have shown that activation of mGlu2 receptors reduces psychosis-like behaviours induced by L-3,4- dihydroxyphenylalanine (L-DOPA) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- lesioned primates. Further insight into the expression and involvement of mGlu2 receptors in mediating such anti-psychotic effects in PD is needed.

Method: Levels of mGlu2 receptors were measured through autoradiographic binding using the mGluR2/3 antagonist [3H]-LY-341,495 as the radioligand, with glutamic acid as the cold ligand. Brain sections from PD patients with VHs, PD patients without VHs, as well as age- and sex-matched healthy controls (N=8 per group) were used for this study. The brain areas examined include the middle temporal gyrus, orbitofrontal cortex, primary motor cortex, caudate nucleus, putamen, nucleus accumbens , thalamus, substantia nigra (both pars compacta and pars reticulata) and globus pallidus (both pars interna and pars externa).

Results: [3H]-LY-341,495 binding levels were increased in the putamen and the internal cortical layer of the medial temporal gyrus, in PD patients without VHs by 25.6% and 26.6% (both areas P < 0.05), respectively, when compared to the control subjects. [3H]-LY-341,495 binding levels were also increased in the external cortical layer of orbitofrontal cortex in PD patients with VHs, by 36.7% (P < 0.05), when compared to the control group. [3H]-LY-341,495 binding levels were not significantly altered in all other brain regions for both PD patients with VHs and PD patients without VHs (P > 0.05).

Conclusion: The results indicate an alteration in mGlu2 binding levels in specific brain regions depending on the presence or absence of VHs in patients with PD. These findings expand our understanding of
the role of mGlu2 receptors in PD and shed light on possible brain areas in which abnormal transmission at mGlu2 receptors may lead to VHs in PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/determination-of-metabotropic-glutamate-receptor-2-3-distribution-with-3h-ly-341495-in-parkinsons-disease-patients-with-visual-hallucinations/