Objective: To determine the distribution of serotonin type 3 (5-HT3) receptors in brain areas implicated in L-3,4-dihydroxyphenylalanine (L-DOPA) induced dyskinesia in the 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson’s disease.
Background: L-DOPA induced dyskinesia is a debilitating treatment-related complication that is estimated to affect nearly all patients with Parkinson’s disease. Recent behavioural studies have found that blockade of the 5-HT3 receptor with the selective antagonists ondansetron and granisetron alleviated dyskinesia in the 6-OHDA rat. Moreover, ondansetron exhibited anti-dyskinetic efficacy in the parkinsonian marmoset. Although these results suggest that 5-HT3 receptor blockade is an effective approach to alleviate dyskinesia, the mechanism of action underlying these therapeutic effects is unclear.
Method: We measured 5-HT3 receptor levels in structures part of the motor loop of the basal ganglia by performing autoradiographic binding using the 5-HT3 antagonist [3H]-GR 65630 and granisetron as the cold ligand. Brain sections were selected from 6-OHDA rats exhibiting mild and severe dyskinesia, L-DOPA-naïve 6-OHDA rats and sham-lesioned animals. Lesion severity was confirmed by tyrosine hydroxylase immunostaining in the striatum.
Results: [3H]-GR 65630 binding of 5-HT3 receptors was significantly increased in the subthalamic nucleus of the lesioned hemisphere of mildly dyskinetic and severely dyskinetic rats compared to L-DOPA-naïve 6-OHDA-lesioned animals (3.17-fold and 3.20-fold, both P < 0.01). [3H]-GR 65630 binding of 5-HT3 receptors in the primary motor cortex and striatum was not significantly altered in L-DOPA treated, mildly dyskinetic or severely dyskinetic 6-OHDA rats compared to sham-lesioned rats (P > 0.05).
Conclusion: Our results suggest that specific brain regions may mediate the anti-dyskinetic efficacy of 5-HT3 antagonists. These findings contribute to our understanding of the role of abnormal 5-HT mediated signalling in L-DOPA induced dyskinesia.
To cite this abstract in AMA style:
C. Kwan, D. Bédard, I. Frouni, A. Hamadjida, P. Huot. Determination of 5-HT3 receptor levels with [3H]-GR 65630 binding in hemi-parkinsonian rats with L-DOPA induced dyskinesia [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/determination-of-5-ht3-receptor-levels-with-3h-gr-65630-binding-in-hemi-parkinsonian-rats-with-l-dopa-induced-dyskinesia/. Accessed June 15, 2025.« Back to MDS Virtual Congress 2021
MDS Abstracts - https://www.mdsabstracts.org/abstract/determination-of-5-ht3-receptor-levels-with-3h-gr-65630-binding-in-hemi-parkinsonian-rats-with-l-dopa-induced-dyskinesia/