Effects of adrenalectomy on pharmacokinetics and antinociceptive activity of morphine in rats.

Abstract

Abstract-The effects of adrenalectomy on the pharmacokinetics and antinocicep tive activity of morphine were investigated to elucidate the mechanism of adre nalectomy-induced potentiation of morphine antinociception in rats. Plasma con centrations of morphine were estimated specifically and serially in each rat by high performance liquid chromatography with an electrochemical detector.After the intravenous administration of 10 mg/kg morphine, the plasma half-life of morphine was significantly prolonged by adrenalectomy without any effect on the volume of morphine distribution.After the subcutaneous administration of 7 mg/kg morphine, pharmacokinetic parameters were changed by adrenalectomy in the same manner as after intravenous administration.In contrast, after the subcutaneous injection of 3.5 mg/kg morphine, adrenalectomy failed to change the pharmacokinetic para meters.The antinociceptive potency of subcutaneously administered morphine was enhanced by adrenalectomy for both doses of morphine (3.5 and 7 mg/kg). Mor phine antinociception at the dose of 3.5 mg/kg, s.c., in the adrenalectomized group was equipotent with that of 7 mg/kg, s.c., in the sham-operated group, but plasma morphine concentrations for 3.5 mg/kg, s.c., in the adrenalectomized group were significantly lower than those for 7 mg/kg morphine, s.c., in the sham-operated group.These results suggest that the enhancement of morphine antinociception by adrenelectomy can not be explained by the increased morphine level alone.

Morphine-Induced Dendritic Spine Remodeling in Rat Nucleus Accumbens Is Corticosterone Dependent

“…Thus, as the animals were treated every day, during 14 days, exactly at the same time of the day, we could speculate that our animals were subjected to a Pavlovian conditioning (Geoffroy et al, 2014), which follows the general laws of learning and thus preferentially involved the shell part of the Nac (Di Chiara and Bassareo, 2007; Marie et al, 2012). Another hypothesis could be that the neuroadaptations observed could be the consequences of the repeated withdrawal periods in our animals, as we used a relatively low dose of morphine (5 mg/kg), with administration once a day, and a half-life of morphine in rats following subcutaneous administration of around 45 minutes (Miyamoto et al, 1988). During the 14 days of treatment, animals certainly have a succession of positive and negative effects that could induce emotional states similar to a chronic stress (Chartoff and Carlezon, 2014).…”