Naltrexone-induced opiate receptor supersensitivity.

Chronic administration of the long-lived narcotic antagonist naltrexone resulted in a marked increase in brain opiate receptors. Similar changes in receptor density were observed for binding of the putative mu agonist [3H]dihydromorphine, the mu antagonist [3H]naloxone, the putative delta ligand [3H]D-Ala2,D-Leu5-enkephalin and [3H]etorphine. In addition, the sensitivity of agonist binding to guanyl nucleotide inhibition increased significantly. In contrast, no such changes in opiate binding were observed following acute administration of naltrexone. The increase in opiate receptor number following chronic naltrexone was highest in the mesolimbic and frontal cortex areas, and lowest in the dorsal hippocampus and periaqueductal gray. These results indicate a degree of plasticity in the opiate receptor system that may correlate with specific functional pathways.