Comparison of opioid and alpha-2 adrenergic receptor binding in horse and dog brain using radioligand autoradiography

Authors

  • Peter W Hellyer DVM, MS, Diplomate ACVA,

    1. Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA
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  • Ling Bai MD, MSc,

    1. Department of Biomedical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA
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  • Julie Supon BS,

    1. Department of Biomedical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA
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  • Cory Quail BS,

    1. Department of Biomedical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA
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  • Ann E Wagner DVM, MS, Diplomate ACVA,

    1. Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA
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  • Khursheed R Mama DVM, Diplomate ACVA,

    1. Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA
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  • Kathy R Magnusson DVM, PhD

    1. Department of Biomedical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA
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    • Current address: Department of Biological Sciences, University of Idaho, Moscow, Idaho.


Peter W Hellyer, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA. E-mail: phellyer@colostate.edu

Abstract

Objective  To test the hypothesis that the distribution, density, and subtype of opioid and alpha (α)-2 adrenergic receptors within the central nervous system (CNS) are significantly different between horse and dog.

Study design  Prospective experimental study.

Animals  Three dogs (3 years of age) and three horses (2–5 years of age). Animals were opioid- and α-2 agonist-free at the time of euthanasia.

Methods  Brain tissue was obtained at 126 days post-surgery from dogs and 72 days post-surgery from horses. The brains were removed, sectioned coronally into 1-cm slabs, frozen in methylbutane, which was cooled by liquid nitrogen, and stored at −70 °C. Receptor autoradiography was performed using established techniques. [3H]DAMGO, [3H]U-69593, and [3H]RX821002 were used for mu (µ)-opioid, kappa (κ)-opioid, and α-2 adrenergic-binding assays, respectively. Species differences were analyzed separately for each major brain region by repeated measures anova for subregions followed by Fisher's protected Latin square design (LSD). p < 0.05 was considered significant.

Results  There was higher binding of µ-opioid receptors in the frontal cortex, left somatosensory cortex, colliculus (mid-brain), and granule cell layer of the cerebellum of horses than that of dogs. There was higher binding to κ-opioid receptors in the frontal cortex of dogs compared to horses, whereas binding to κ-opioid receptors in the cerebellum was higher in horses. Binding to α-2 adrenergic receptors in the mid-brain was significantly higher in dogs than in horses. There was higher binding of α-2 adrenergic receptors in the dorsomedial and dorsolateral periaqueductal grey of dogs as compared to that of horses.

Conclusion  The results of this study show that the distribution of these receptors is different between horses and dogs. Further work is needed to understand the relevance of these differences to clinical responses to opioids and α-2 adrenergic agonists in these species.

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