Quantitative autoradiography of μ-,δ- and κ1 opioid receptors in κ-opioid receptor knockout mice |
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Authors: | Susan J. Slowe Frederic Simonin Brigitte Kieffer Ian Kitchen |
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Affiliation: | a Pharmacology Research Group, School of Biological Sciences, University of Surrey, Guildford, Surrey, GU2 5XH, UK;b UPR 9050 CNRS, ESBS Universite Louis Pasteur, 67400 Illkirch, Strasbourg, France |
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Abstract: | Mice deficient in the κ-opioid receptor (KOR) gene have recently been developed by the technique of homologous recombination and shown to lack behavioural responses to the selective κ1-receptor agonist U-50,488H. We have carried out quantitative autoradiography of μ-, δ- and κ1 receptors in the brains of wild-type (+/+), heterozygous (+/−) and homozygous (−/−) KOR knockout mice to determine if there is any compensatory expression of μ- and δ-receptor subtypes in mutant animals. Adjacent coronal sections were cut from the brains of +/+, +/− and −/− mice for the determination of binding of [3H]CI-977, [3H]DAMGO ( -Ala2-MePhe4-Gly-ol5 enkephalin) or [3H]DELT-I ( -Ala2 deltorphin I) to κ1-, μ- and δ-receptors, respectively. In +/− mice there was a decrease in [3H]CI-977 binding of approximately 50% whilst no κ1-receptors could be detected in any brain region of homozygous animals confirming the successful disruption of the KOR gene. There were no major changes in the number or distribution of μ- or δ-receptors in any brain region of mutant mice. There were, however some non-cortical regions where a small up-regulation of δ-receptors was observed in contrast to an opposing down-regulation of δ-receptors evident in μ-knockout brains. This effect was most notable in the nucleus accumbens and the vertical limb of the diagonal band, and suggests there may be functional interactions between μ- and δ-receptors and κ1- and δ-receptors in mouse brain. |
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Keywords: | κ -Knockout Knockout mouse KOR gene Opioid receptor μ -Receptor δ -Receptor κ -Receptor Autoradiography Gene deletion |
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