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

Autor: Luc Zimmer, Adrian Newman-Tancredi, Sarah Chaib, Benjamin Vidal, Caroline Bouillot, Thierry Billard, Elise Levigoureux
Přispěvatelé: Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2021
Předmět:
0301 basic medicine
Agonist
Dyskinesia
Drug-Induced
medicine.medical_specialty
Parkinson's disease
medicine.drug_class
Stimulation
Serotonin 5-HT1 Receptor Antagonists
Antiparkinson Agents
Levodopa
03 medical and health sciences
Cellular and Molecular Neuroscience
chemistry.chemical_compound
GPCR
0302 clinical medicine
Dopamine
Internal medicine
medicine
Animals
Levodopa-induced dyskinesia
business.industry
Parkinson Disease
Serotonin 5-HT1 Receptor Agonists
medicine.disease
Rats
serotonin
nervous system diseases
Disease Models
Animal
030104 developmental biology
Endocrinology
nervous system
chemistry
Dyskinesia
Receptor
Serotonin
5-HT1A
5-HT1A receptor
5-HT1A
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Neurology (clinical)
MPPF
medicine.symptom
business
030217 neurology & neurosurgery
medicine.drug
Zdroj: Journal of Parkinson's disease
Journal of Parkinson's disease, Amsterdam : b : IOS Press, 2021, 11 (3), pp.1257-1269. ⟨10.3233/JPD-212580⟩
ISSN: 1877-718X
1877-7171
Popis: International audience; 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.
Databáze: OpenAIRE
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