Quantitative autoradiography of μ-, δ- and κ1 opioid receptors in κ-opioid receptor knockout mice

Mice deficient in the K-opioid receptor (KOR) gene have recently been developed by the technique of homologous recombination and shown to lack behavioural responses to the selective (kappa)1-receptor agonist U-50,488H. We have carried out quantitative autoradiography of mu-, delta- and kappa(1) receptors in the brains of wild-type (+ / +), heterozygous (+ / -) and homozygous (- / -) KOR knockout mice to determine if there is any compensatory expression of mu- and delta-receptor subtypes in mutant animals. Adjacent coronal sections were cut from the brains of + / +, + / - and - / - mice far the determination of binding of [H-3]CI-977, [H-3]DAMGO (D-Ala(2)-MePhe(4)-Gly-ol(5) enkephalin) or [H-3]DELT-I (D-Ala(2) deltorphin I) to kappa(1)-, mu- and delta-receptors, respectively. In + / - mice there was a decrease in [H-3]CI-977 binding of approximately 50% whilst no kappa(1)-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 mu- or delta-receptors in any brain region of mutant mice. There were, however some non-cortical regions where a small up-regulation of delta-receptors was observed in contrast to an opposing down-regulation of delta-receptors evident in mu-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 mu- and delta-receptors and kappa(1)- and delta-receptors in mouse brain. (C) 1999 Elsevier Science B.V. All rights reserved.