Department of Clinical Sciences
Contact Information: Email: email@example.com; Phone: 607-253-4220
Sponsor: Association of Avian Veterinarians
Grant Number: N/A
Title: Comparative Immunohistochemical Localization and Characterization of the Mu and Kappa Opioid Receptors in Selected Raptor, Psittacine, Waterfowl and Passerine Species
Annual Direct Cost: $8,942
Project Period: 09/01/2011-08/31/2012
DESCRIPTION (provided by applicant): Opioid analgesics are a group of drugs that bind reversibly to receptors in the brain and spinal cord of vertebrates. Clinical use of opioid analgesics in birds has been validated in selected species and opioids are considered the most effective drugs to control pre and post-operative pain. Studies in chickens, African grey and Hispaniolan Amazon parrots, red-tailed hawks, and great-horned owls have illustrated that pharmacokinetics, metabolism, and analgesic effect of opioids in these different species vary greatly. It is possible the variation in analgesic effect is due not only to differences in drug metabolism but also to the prevalence and distribution of different opioid receptors in the CNS, which is unknown for the majority of bird species. Early studies in the distribution of mu, delta, and kappa opioid receptors in the forebrains of humans, rats, monkeys, mice, guinea pigs, and pigeons showed that there is great variety in the predominance of different receptor types in the forebrains of different species. The presence of opioid receptors in the avian forebrain has only been described in pigeons, chickens and zebra finches (Csillag et al 1990; Reiner et al 1989, Kawate et al 2005, Khurshid et al 2009). It is believed that other avian species have mu, kappa and delta opioid receptors considering the reported subjective and objective clinical responses to opioid administration. Therefore, mapping the distribution of mu and kappa opioid receptors in the avian forebrain and midbrain is important to further understand and predict opioid analgesic effects across species and to enhance clinical opioid analgesia in birds.
We propose to characterize CNS mu and kappa opioid receptor distribution in representative raptor (red-tailed hawk, great horned owl, American kestrel), psittacine (Amazon parrot, umbrella cockatoo), anseriform (mallard duck, Canada goose), and passerine (starling, crow) species using immunohistochemistry (IHC). Mu and kappa receptors will be investigated since these are the most relevant for analgesia. Despite the lack of commercially available antibodies against opioid receptors in birds, there is a 96% homology between the human and chicken mu receptor amino acid sequence. The sequence of this receptor is also highly conserved across species (Khurshid et al 2009) and mammalian antibodies have been used successfully to localize mu and delta opioid receptors using IHC in avian species (Kawate et al 2005, Khurshid et al 2009).
The objectives of this study are to:
I. Optimize an immunohistochemistry (IHC) protocol for mu and kappa opioid receptors in chickens and zebra finches, species in which the technique was used and distribution of mu receptors within certain regions of the brain is known (Kawate et al 2005, Khurshid et al 2009).
II. To use the IHC protocol optimized in objective I for characterization of mu and kappa receptors distribution in several avian species
No birds will be purposely purchased or maintained for this study. Tissues will be obtained from the archives of the Cornell College of Veterinary Medicine Section of Anatomic Pathology as well as prospectively collected from animals presenting for necropsy from Cornell University College of Veterinary Medicine Zoological Medicine Service and University of California Davis School of Veterinary Medicine.