Skip to Main content Skip to Navigation
Theses

La neuroimagerie TEP-IRM pour l'exploration de l'agonisme des récepteurs 5-HT1A

Abstract : Since the 1990s, PET imaging of 5-HT1A receptors has led to an increased understanding of the pathophysiological role of these receptors. However, the coupling between 5-HT1A receptors and G-proteins, which may be altered during pathologies, cannot be explored using current radiotracers. The work carried out in this thesis aims to promote the use of translational imaging techniques to explore the coupling of 5-HT1A receptors in vivo. In the first part, we evaluated the 5-HT1A receptor agonist F13640 as a PET radiotracer candidate. Taken together, the results suggest that [18F]F13640 binds specifically to coupled 5-HT1A receptors and displays novel properties and distribution pattern compared to classical 5-HT1A radiotracers. The second part was a proof-of-concept study regarding the interest of coupled 5-HT1A receptors imaging. Densities of coupled and total receptors were compared in postmortem autoradiography during Alzheimer’s disease. [18F]F13640 binding in hippocampus was decreased in the early stages, whereas [18F]MPPF binding was reduced in the advanced stages only. These results confirm the complementarity between 5-HT1A receptor agonists and antagonist tracers in PET imaging.In the last part we focused on the concept of biased agonism, which implies the possibility of targeting different populations of 5-HT1A receptors depending on their coupling with G-proteins. F13640 and F15599 were compared at pharmacological doses using PET and fMRI imaging. The two agonists produce different hemodynamic and metabolic responses in rat brain. They also differ in cat brain in terms of receptor occupancy and subsequent hemodynamic responses. Taken together, the results are consistent with a preferential stimulation of postsynaptic receptors over autoreceptors for F15599, in contrast with F13640
Document type :
Theses
Complete list of metadatas

Cited literature [453 references]  Display  Hide  Download

https://tel.archives-ouvertes.fr/tel-01891070
Contributor : Abes Star :  Contact
Submitted on : Tuesday, October 9, 2018 - 11:29:34 AM
Last modification on : Thursday, November 21, 2019 - 2:09:56 AM
Long-term archiving on: : Thursday, January 10, 2019 - 2:24:47 PM

File

TH2017VIDALBENJAMIN.pdf
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-01891070, version 1

Citation

Benjamin Vidal. La neuroimagerie TEP-IRM pour l'exploration de l'agonisme des récepteurs 5-HT1A. Neurosciences [q-bio.NC]. Université de Lyon, 2017. Français. ⟨NNT : 2017LYSE1235⟩. ⟨tel-01891070⟩

Share

Metrics

Record views

176

Files downloads

818