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Article type: Research Article
Authors: Vidal, Benjamina; 1 | Levigoureux, Elisea; b; 1 | Chaib, Saraha; b | Bouillot, Carolinec | Billard, Thierryc; d | Newman-Tancredi, Adriane | Zimmer, Luca; b; c; *
Affiliations: [a] Lyon Neuroscience Research Center, Université de Lyon, Université Claude Bernard Lyon 1, CNRS, INSERM, Lyon, France | [b] Hospices Civils de Lyon, Lyon, France | [c] CERMEP-Imaging Platform, Bron, France | [d] Institute of Chemistry and Biochemistry, Université de Lyon, CNRS, Villeurbanne, France | [e] Neurolixis SAS, Castres, France
Correspondence: [*] Correspondence to: Prof. Luc Zimmer, Lyon Neuroscience Research Center, Université de Lyon, Université Claude Bernard Lyon 1, CNRS UMR5292, INSERM U1028, Lyon, France. Tel.: +33 4 72 68 86 09; E-mail: [email protected].
Note: [1] These authors contributed equally to this work.
Abstract: Background:The gold-standard treatment for Parkinson’s disease is L-DOPA, which in the long term often leads to levodopa-induced dyskinesia. Serotonergic neurons are partially responsible for this, by converting L-DOPA into dopamine leading to its uncontrolled release as a “false neurotransmitter”. The stimulation of 5-HT1A receptors can reduce involuntary movements but this mechanism is poorly understood. Objective:This study aimed to investigate the functionality of 5-HT1A receptors using positron emission tomography in hemiparkinsonian rats with or without dyskinesia induced by 3-weeks daily treatment with L-DOPA. Imaging sessions were performed “off” L-DOPA. Methods:Each rat underwent a positron emission tomography scan with [18F]F13640, a 5-HT1AR agonist which labels receptors in a high affinity state for agonists, or with [18F]MPPF, a 5-HT1AR antagonist which labels all the receptors. Results:There were decreases of [18F]MPPF binding in hemiparkinsonian rats in cortical areas. In dyskinetic animals, changes were slighter but also found in other regions. In hemiparkinsonian rats, [18F]F13640 uptake was decreased bilaterally in the globus pallidus and thalamus. On the non-lesioned side, binding was increased in the insula, the hippocampus and the amygdala. In dyskinetic animals, [18F]F13640 binding was strongly increased in cortical and limbic areas, especially in the non-lesioned side. Conclusion:These data suggest that agonist and antagonist 5-HT1A receptor-binding sites are differently modified in Parkinson’s disease and levodopa-induced dyskinesia. In particular, these observations suggest a substantial involvement of the functional state of 5-HT1AR in levodopa-induced dyskinesia and emphasize the need to characterize this state using agonist radiotracers in physiological and pathological conditions.
Keywords: 5-HT1A, Parkinson’s disease, serotonin, levodopa-induced dyskinesia, GPCR
DOI: 10.3233/JPD-212580
Journal: Journal of Parkinson's Disease, vol. 11, no. 3, pp. 1257-1269, 2021
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