Effects of chronic drug treatment on the sensitivity of mouse vas deferens to drugs

Abstract

Chronic treatment of mice with clonidine or morphine reduced the sensitivity of the isolated, field-stimulated, vas deferens to the inhibitory effects of acutely administered clonidine and morphine. Chronic treatment of mice with clonidine produced a postsynaptic non-specific supersensitivity to noradrenaline and carbachol, but not to potassium chloride. Chronic treatment with morphine produced a specific supersensitivity to noradrenaline. Chronic treatment of mice with naloxone increased the sensitivity of the isolated, field stimulated, vas deferens to the inhibitory effects of acutely administered morphine, but not to clonidine. Naloxone treatment of mice did not affect the sensitivity of the isolated vas deferens to noradrenaline, carbachol or potassium chloride. These results suggest a physiological role for the opioid receptors in the mouse vas deferens and an apparent cross-tolerance between clonidine and morphine. The possible mechanisms are discussed.