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Amphetamine challenge decreases yohimbine binding to α2 adrenoceptors in Landrace pig brain

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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.

Conflicts of interest

Authors have no financial conflicts of interest.

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Authors and Affiliations

  1. Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Norrebrogade 44, Building 10G, Aarhus C, 8000, Denmark

    Anne M. Landau, Doris J. Doudet & Steen Jakobsen

  2. Center of Functionally Integrative Neuroscience, Aarhus University Hospital, Aarhus, Denmark

    Anne M. Landau & Doris J. Doudet

  3. Department of Medicine/Neurology, University of British Columbia, Vancouver, BC, Canada

    Doris J. Doudet

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  1. Anne M. Landau
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Correspondence to Steen Jakobsen.

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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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