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The Journal of Neuroscience, November 1, 2002, 22(21):9210-9220

Changes in Spinal delta  and kappa  Opioid Systems in Mice Deficient in the A2A Receptor Gene

Alexis Bailey1, Catherine Ledent2, Mary Kelly1, Susanna M. O. Hourani1, and Ian Kitchen1

1 Pharmacology Group, School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey, GU2 7XH United Kingdom, and 2 Institut de Recherche Interdisciplinaire en Biologie Humaine et Nucléaire, Université Libre de Bruxelles, B-1070 Brussels, Belgium

A large body of evidence indicates important interactions between the adenosine and opioid systems in regulating pain at both the spinal and supraspinal level. Mice lacking the A2A receptor gene have been developed successfully, and these animals were shown to be hypoalgesic. To investigate whether there are any compensatory alterations in opioid systems in mutant animals, we have performed quantitative autoradiographic mapping of µ, delta , kappa , and opioid receptor-like (ORL1) opioid receptors in the brains and spinal cords of wild-type and homozygous A2A receptor knock-out mice. In addition, µ-, delta -, and kappa -mediated antinociception using the tail immersion test was tested in wild-type and homozygous A2A receptor knock-out mice. A significant reduction in [3H]deltorphin-I binding to delta  receptors and a significant increase in [3H]CI-977 binding to kappa  receptors was detected in the spinal cords but not in the brains of the knock-out mice. µ and ORL1 receptor expression were not altered significantly. Moreover, a significant reduction in delta -mediated antinociception and a significant increase in kappa -mediated antinociception were detected in mutant mice, whereas µ-mediated antinociception was unaffected. Comparison of basal nociceptive latencies showed a significant hypoalgesia in knock-out mice when tested at 55°C but not at 52°C. The results suggest a functional interaction between the spinal delta  and kappa  opioid and the peripheral adenosine system in the control of pain pathways.

Key words: A2A knock-out; µ opioid receptor; delta opioid receptor; kappa opioid receptor; ORL1 receptor; autoradiography; opioid-mediated antinociception


Copyright © 2002 Society for Neuroscience  0270-6474/02/22219210-11$05.00/0


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[Abstract] [Full Text] [PDF]



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