Differential regulation of mu-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 mu-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 mu-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 mu-opiate receptors may underlie differences in the behavioral and pharmacological profiles of heroin and morphine reported in man.
Bolger
G T
GT
Laboratory of Neuroscience, NIDDK, Bethesda, MD 20892.
Skolnick
P
P
Rice
K C
KC
Weissman
B A
BA
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004090:Dihydromorphine / Q000378:metabolism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000378:metabolism; D003932:Heroin; D008297:Male; D009020:Morphine; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D017450:Receptors, Opioid, mu; D012964:Sodium / Q000494:pharmacology; D019966:Substance-Related Disorders / Q000378:metabolism*
D004745:Enkephalins; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D003932:Heroin; D009020:Morphine; D012964:Sodium; D004090:Dihydromorphine