Spontaneous withdrawal in intermittent morphine administration in rats and mice: effect of clonidine coadministration and sex-related differences.

Background/aim: Treating animals repeatedly with intermittent and increasing morphine doses has been suggested to allow some withdrawal during each dosing interval, which causes repeated stress. The present study aimed to test this hypothesis and assess sex-related differences in withdrawal signs and their suppression by clonidine.

Materials And Methods: Male and female rats and mice were administered with increasing doses of morphine twice daily at different dosing intervals.