In Vitro Morphine Binding by Sera from Morphine-Treated Rabbits

Abstract Results of a number of studies on the development of tolerance to morphine suggest that at least some aspects of this tolerance are immunologic-like in character (for reviews see Friedler (1) and Cochin (2)). Evidence that the morphine configuration is immunogenic is provided by Ryan et al. (3) who recently reported the apparent presence of antibody against morphine in the sera of approximately 40% of heroin addicts studied. Preliminary findings from our laboratory, in studies reported here, have indicated that in the rabbit prolonged exposure to morphine is associated with an increase in serum binding of 14C-labeled morphine, both after withdrawal from morphine and after a brief re-exposure to morphine. Two albino New Zealand female rabbits were given multiple doses of morphine sulfate or morphine hydrochloride (Merck, USP) administered subcutaneously in three courses of injections spaced 1 and 2 months apart. Except for some initial and terminal injections, morphine doses were routinely given twice daily beginning with a dose level (base weight, b.w.) of 8 mg morphine/kg b.w. and progressing incrementally to dose levels ranging from 40 to 64 mg/kg b.w. The periods covered for each course of injections were 6 to 23 days per course for rabbit 1 and 10 days per course for rabbit 2.