Opiate receptor binding-enhancement by opiate administration in vivo

Administration of opiate agonists and antagonists to mice produces a dose-dependent 50-100 per cent enhancement of stereospecific [³H]dihydromorphine or [³H]naloxone binding to brain homogenates within 5 min. Three opiate antagonists are 10-1000 times more potent in eliciting this increase in binding than their structurally analogous agonists. Naloxone, the antagonist with the least agonist activity, is the most potent drug in producing receptor enhancement. Implantation of morphine pellets in mice increases receptor binding 30-100 per cent for 2 108 hr with no time-dependent trend. Drug-induced receptor binding enhancement appears to involve an increase in number of binding sites rather than a change in receptor affinity. Sodium, which increases binding of opiate antagonists in normal mouse brain homogenate, fails to increase binding of [³H]naloxone in homogenates derived from naloxone-injected mice.