In vivo opiate binding unchanged in tolerant/dependent mice.

The in vivo receptor binding was measured for an opiate agonist and antagonist in the brains of naive mice and of mice made tolerant to and dependent on opiates by morphine pretreatment. There was significant differences between the receptor binding of these substances in the naive and in the tolerant/dependent animals. However, these differences disappeared 8 h after interruption of the morphine supply, although tolerance showed no decline. Therefore, the differences in the binding were obviously not produced by changes in the opiate receptors related to tolerance. Rather, the differences were probably caused by morphine in the brain of the tolerant/dependent mice pretreated with morphine and disappeared because the concentration of the morphine in the brains of these animals dropped during abrupt withdrawal. The fact that tolerance persisted for hours beyond this time indicated that tolerance is a time-dependent phenomenon, not directly dependent on receptor occupation by an agonist.