Autoradiographic labelling of 5-HT3 receptors in the hemi-parkinsonian rat brain. (April 2022)

• Record Type: Journal Article
• Authors: Kwan, Cynthia; Lévesque, Catherine; Bédard, Dominique; Frouni, Imane; Yesuf, Jemal M; Hamadjida, Adjia; Lévesque, Daniel; Clarke, Paul BS; Huot, Philippe
• Is Part Of: Neuroscience research. Volume 177(2022)
• Page Start: 135
• Page End: 144
• Publication Date: 2022-04
• Subjects: 5-HT3 receptor -- Parkinson's disease -- Dyskinesia -- Granisetron -- [3H]GR65630 -- Autoradiography; Neurosciences -- Research -- Periodicals; Neurosciences -- Research -- Japan -- Periodicals; Neurology -- Periodicals; Neurosciences -- Periodicals; Neurosciences -- Recherche -- Périodiques; Neurosciences -- Recherche -- Japon -- Périodiques; Neurosciences -- Research; Japan; Periodicals; 612.8
• DOI: 10.1016/j.neures.2021.12.004
• Languages: English
• ISSNs: 0168-0102

Abstract

Highlights: Mechanism underlying anti-dyskinetic efficacy of 5-HT3 receptor antagonists is unclear. Dyskinetic hemi-parkinsonian rats showed increased 5-HT3 levels in the STN, EP and thalamus. Dyskinesia severity negatively correlated with 5-HT3 levels in the striatum and STN. Changes in 5-HT3 levels in the basal ganglia may modulate l -DOPA induced dyskinesia. Abstract: L-3, 4-dihydroxyphenylalanine (l -DOPA) is the mainstay treatment for Parkinson's disease, but its effectiveness during early disease is marred by the eventual development of l -DOPA induced dyskinesia. In hemi-parkinsonian rats, the serotonin type 3 (5-HT3 ) antagonists ondansetron and granisetron alleviated dyskinesia induced by l -DOPA without impeding its anti-parkinsonian action; in parkinsonian marmosets, ondansetron alleviated dyskinesia and enhanced l -DOPA anti-parkinsonian action. Here, we sought to gain insight into the mechanisms governing the anti-dyskinetic action of 5-HT3 antagonists and measured 5-HT3 receptor levels across different brain, using [ 3 H]GR65630 autoradiographic binding. Brain sections were chosen from 6-hydroxydopamine (6-OHDA)-lesioned rats exhibiting abnormal involuntary movements (AIMs), as well as l -DOPA-naïve 6−OHDA and sham-lesioned animals. [ 3 H]GR65630 binding increased in the ipsilateral subthalamic nucleus of 6-OHDA-lesioned rats with mild and severe AIMs, (3-fold changes, P < 0.001). [ 3 H]GR65630 binding also increased in the ipsilateral entopeduncular nucleus and thalamus of 6-OHDA-lesioned rats with severe AIMs (75 % and 88 %, P < 0.05). AIMs scores negatively correlated with [ 3 H]GR65630 binding in the ipsilateral dorsolateral striatum and contralateral subthalamic nucleus ( P < 0.05). These results suggest that alterations in 5-HT3 mediated neurotransmission may contribute to the pathophysiology of l -DOPA induced dyskinesia.