| Summary: | 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 [<sup>11</sup>C]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 [<sup>11</sup>C]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. [<sup>11</sup>C]yohimbine volumes of distribution (V<sub>T</sub>) were obtained using the Logan kinetic model. Both challenges induced a significant decrease in yohimbine V<sub>T</sub>, 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 V<sub>T</sub>. These data suggest that [<sup>11</sup>C]yohimbine can be used to evaluate acute variations in synaptic noradrenaline concentrations after pharmacological challenges.
|
|---|