Differential regulation of μ-opiate receptors in heroin- and morphine-dependent rats

Rats made dependent on heroin and morphine exhibit both qualitative and quantitative differences in the characteristics of radioligand binding to μ-opioid receptors in the central nervous system. In brain membranes prepared from control animals, [ 3H]dihydromorphine (DHM) binding was best described by a two-site model, while in morphine-dependent rats, [ 3H]DHM binding was best described by a single-site model. In contrast, [ 3H]DHM binding to membranes from heroin-dependent animals was best described by a two-site model, with an increased density of the high-affinity, and no change in the low-affinity population compared to controls. Furthermore, both the number of binding sites for [ 3H]DAGO (a ligand that selectively labels a population of high-affinity μ-opiate receptors) and the sensitivity of [ 3H]DHM to sodium ions was increased in heroin; but not in morphine-dependent rats. These studies demonstrate that opiate receptors are differentially regulated in heroin- and morphine-dependent animals. Such neurochemical changes in μ-opiate receptors may underlie differences in the behavioral and pharmacological profiles of heroin and morphine reported in man.