Quantitative autoradiography of mu-, delta- and kappa(1) opioid receptors in kappa-opioid receptor knockout mice

Mice deficient in the K-opioid receptor (KOR) gene have recently been devel oped by the technique of homologous recombination and shown to lack behavio ural responses to the selective (kappa)1-receptor agonist U-50,488H. We hav e carried out quantitative autoradiography of mu-, delta- and kappa(1) rece ptors in the brains of wild-type (+ / +), heterozygous (+ / -) and homozygo us (- / -) KOR knockout mice to determine if there is any compensatory expr ession of mu- and delta-receptor subtypes in mutant animals. Adjacent coron al 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 succes sful 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 mic e. There were, however some non-cortical regions where a small up-regulatio n of delta-receptors was observed in contrast to an opposing down-regulatio n of delta-receptors evident in mu-knockout brains. This effect was most no table in the nucleus accumbens and the vertical limb of the diagonal band, and suggests there may be functional interactions between mu- and delta-rec eptors and kappa(1)- and delta-receptors in mouse brain. (C) 1999 Elsevier Science B.V. All rights reserved.