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Combined In Vivo Microdialysis and PET Studies to Validate [11C]Yohimbine Binding as a Marker of Noradrenaline Release.
| Content Provider | Europe PMC |
|---|---|
| Author | Landau, Anne Marlene Jakobsen, Steen Thomsen, Majken Borup Alstrup, Aage Kristian Olsen Orlowski, Dariusz Jacobsen, Jan Wegener, Gregers Mørk, Arne Sørensen, Jens Christian Hedemann Doudet, Doris J. |
| Editor | Boutin, Hervé |
| Copyright Year | 2023 |
| Abstract | The noradrenaline system attracts attention for its role in mood disorders and neurodegenerative diseases but the lack of well-validated methods impairs our understanding when assessing its function and release in vivo. This study combines simultaneous positron emission tomography (PET) and microdialysis to explore if [11C]yohimbine, a selective antagonist radioligand of the α2 adrenoceptors, may be used to assess in vivo changes in synaptic noradrenaline during acute pharmacological challenges. Anesthetised Göttingen minipigs were positioned in a head holder in a PET/CT device. Microdialysis probes were placed in the thalamus, striatum and cortex and dialysis samples were collected every 10 min. Three 90 min [11C]yohimbine scans were acquired: at baseline and at two timepoints after the administration of amphetamine (1–10 mg/kg), a non-specific releaser of dopamine and noradrenaline, or nisoxetine (1 mg/kg), a specific noradrenaline transporter inhibitor. [11C]yohimbine volumes of distribution (VT) were obtained using the Logan kinetic model. Both challenges induced a significant decrease in yohimbine VT, with time courses reflecting their different mechanisms of action. Dialysis samples revealed a significant increase in noradrenaline extracellular concentrations after challenge and an inverse correlation with changes in yohimbine VT. These data suggest that [11C]yohimbine can be used to evaluate acute variations in synaptic noradrenaline concentrations after pharmacological challenges. |
| Journal | Biomolecules |
| Volume Number | 13 |
| PubMed Central reference number | PMC10136072 |
| Issue Number | 4 |
| PubMed reference number | 37189421 |
| e-ISSN | 2218273X |
| DOI | 10.3390/biom13040674 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2023-04-14 |
| Access Restriction | Open |
| Rights License | Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). © 2023 by the authors. |
| Subject Keyword | a2 adrenoceptors noradrenaline microdialysis minipig positron emission tomography [11C]yohimbine |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biochemistry Molecular Biology |
