CNS distribution of D1 receptors: Use of a new specific D1 receptor antagonist, [3H]SCH39166

Abstract D 1 dopamine receptors have been localized using a radioactive form of a new specific antagonist, [ 3 H]SCH39166. This compound has been shown, in in vitro binding studies, to be highly selective for the D 1 receptor subtype; more so than its predecessor, [ 3 H]SCH23390. These ligand binds saturably, reversibly and with high affinity. Use of appropriate conditions produces a high signal to noise binding ratio to D 1 receptors in slide-mounted tissue sections. Autoradiographic localization of radiolabeled receptors shows high densities of the D 1 receptor subtype in such brain structures as the caudate-putamen, nucleus accumbens, entopeduncular nucleus, and the substantia nigra pars reticulata. A lower density ofreceptors is found in a few other areas including lamina VI of the cerebral cortex. A distinct paucity of binding was apparent in lamina IV of the cerebral cortex and in the choroid plexus, two areas thought to have D 1 receptors. SCH39166 thus represents a superior ligand for obtaining selective labeling of D 1 receptors in autoradiographic and binding studies.