Abstract
Rationale
The noradrenaline (NA) system is implicated in neurodegenerative and psychiatric disorders; however, our understanding is impaired by the lack of well-validated radioligands to assess NA function and release. Yohimbine, an α2 adrenoceptor antagonist, has recently been developed as a carbon-11 [11C]-labeled radioligand for positron emission tomography (PET) imaging studies.
Objectives
Here we explore the hypothesis that yohimbine can be used as an in vivo tracer of NA receptor binding and release during amphetamine challenges in Landrace pigs.
Methods
Pigs underwent baseline PET scans with [11C]yohimbine and were then challenged with 10 mg/kg d-amphetamine 20 min prior to a second [11C]yohimbine scan. Using the Logan analysis model, volumes of distribution were calculated from fits of the kinetic data 25–90 min post-yohimbine injection.
Results
Amphetamine decreased [11C]yohimbine volume of distribution in the brain regions under investigation, including the thalamus, caudate nucleus, and cortical regions.
Conclusion
These data suggest that the binding of [11C]yohimbine to α2 adrenoceptors may be displaceable by increases in synaptic concentrations of the endogenous ligand, NA, and possibly dopamine, suggesting the possibility that [11C]yohimbine may be used as a surrogate marker of NA release in vivo.
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Acknowledgments
This work was supported by grants from Denmark’s National Science Foundation and The Danish Medical Research Council. “Principles of laboratory animal care” were followed, and all experiments were performed according to Danish regulations. We thank Aage Alstrup for skillful assistance with the care of the pigs during the PET studies, and we are grateful to the staff at the PET center for technical assistance.
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Landau, A.M., Doudet, D.J. & Jakobsen, S. Amphetamine challenge decreases yohimbine binding to α2 adrenoceptors in Landrace pig brain. Psychopharmacology 222, 155–163 (2012). https://doi.org/10.1007/s00213-011-2632-6
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DOI: https://doi.org/10.1007/s00213-011-2632-6