Chronic morphine upregulates a μ-opiate binding site labeled by [ 3H]cycloFOXY: a novel opiate antagonist suitable for positron emission tomography

Abstract

CycloFOXY (17-cyclopropylmethyl-3,14-dihydroxy-4,5-α-epoxy-6-β-fluoromorphinan) is a novel opiate antagonist synthesized as a ligand suitable for in vivo visualization of opiate receptors using positron emission transaxial tomography. In this paper we report that [ 3H]cycloFOXY labels two distinct opiate binding sites in rat brain membranes, tentatively identified as μ and κ. Furthermore, chronic administration of morphine results in a selective up-regulation of the μ binding site. The implications of this finding for models of the opioid receptors and the mechanism of the sodium effect are discussed.