Opioid receptors: From genes to mice

opiates produce their strong analgesic and addictive actions by activating mu-, delta-, and kappa-opioid receptors, which otherwise interact with endo genous opioid peptides to regulate nociception, mood, and responses to stre ss. The recent cloning of an opioid receptor gene family has allowed the pr oduction of null-mutant mice for each mu-, delta-, and kappa-receptor gene. Initial observation of receptor-deficient mice shows no obvious developmen tal abnormality, and reveals subtle modifications of pain perception in adu lt mice. Pharmacologic responses to standard opiates have been evaluated ca refully and results suggest that morphine produces its main biologic action s by acting specifically at mu-receptors, whereas delta-agonists seem weakl y delta-selective under in vivo experimental conditions. Future studies of single- and combinatorial-opioid receptor-deficient mice will clarify the s pecific role of each receptor in chronic pain, motivation, and addictive be haviors. These mice also represent useful tools in the development of novel opioid compounds of therapeutic interest.