Reduction of opiate binding to brainstem slices associated with the development of tolerance to morphine in rats.

Previous studies revealed that the characteristics of opiate binding sites are different in brainstem slices and homogenates. In the present study, the binding of opiate agonists, morphine and etorphine, and that of the antagonist, naloxone, to thin slices of rat brain stem was studied. Sodium ion inhibits agonist binding and enhances antagonist binding in brainstem slices. Development of the analgesic tolerance to morphine is accompanied by a reduction of opiate binding. The opiate binding recovers partially toward control values during morphine withdrawal. Kinetic analyses indicate that sodium-induced changes in opiate binding sites are different from those caused by chronic morphine treatment. These results provide evidence that analgesic tolerance is associated with changes in opiate receptors.