Autoradiographic mapping of the opioid receptor-like 1 (ORL1) receptor in the brains of mu-, delta- or kappa-opioid receptor knockout mice

The opioid receptor-like 1 (ORL1) receptor shares a high degree of sequence homology with the classical mu-, delta- and kappa -opioid receptors and a functional mutual opposition between these receptors has been suggested, To further address this possible interaction we have used mu-, delta- and kap pa -opioid receptor knockout mice to determine autoradiographically if ther e are any changes in the number or distribution of the ORL1 receptor, label led with [H-3]nociceptin, in the brains of mice deficient in each of the op ioid receptors. An up-regulation of ORL1 expression was observed across all brain regions in delta -knockouts with cortical regions typically showing a 15-30% increase in binding that was most marked in heterozygous mice. In contrast, ORL1 receptor expression was down-regulated in virtually all brai n structures in heterozygous kappa -knockouts although the magnitude of thi s change was not as great as for the delta -knockouts. No significant alter ations in ORL1 receptor expression were observed across brain regions in de lta -receptor knockout mice and there were no qualitative differences in OR L1 receptor expression in any groups. These data suggest there are interactions between the ORL1 system and the c lassical opioid receptors and that the interactions are receptor-specific, The greater differences observed in heterozygous mice suggest that these in teractions might be most relevant when there is only partial loss of recept or function. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights r eserved.