Different alterations of agonist and antagonist binding to 5-HT1A receptor in a rat model of Parkinson's disease and levodopa-induced dyskinesia : a microPET study

Benjamin Vidal (1) , Elise Levigoureux (1) , Sarah Chaib (1) , Caroline Bouillot (2) , Thierry Billard (3) , Adrian Newman-Tancredi , Luc Zimmer (2)

1 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
2 CERMEP - imagerie du vivant - Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant
3 ICBMS - Institut de Chimie et Biochimie Moléculaires et Supramoléculaires

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.

Mots clés: 5-HT1A; Parkinson's disease; serotonin; Levodopa-induced dyskinesia; GPCR

Domaines: Neurosciences [q-bio.NC]

Benjamin Vidal, Elise Levigoureux, Sarah Chaib, Caroline Bouillot, Thierry Billard, et al.. Different alterations of agonist and antagonist binding to 5-HT1A receptor in a rat model of Parkinson's disease and levodopa-induced dyskinesia : a microPET study. Journal of Parkinson's disease, 2021, 11 (3), pp.1257-1269. ⟨10.3233/JPD-212580⟩. ⟨hal-03407557⟩