IMMUNOHISTOCHEMICAL LOCALIZATION OF ORL-1 IN THE CENTRAL-NERVOUS-SYSTEM OF THE RAT

A novel member of the opioid receptor family (ORL-1) has been cloned f rom a variety of vertebrates. ORL-1 does not bind any of the classical opioids, although a high affinity endogenous agonist with close homol ogy to dynorphin has recently been identified. We have generated a mon oclonal antibody to the N-terminus of ORL-1 to map areas of receptor e xpression in rat central nervous system (CNS). Intense and specific im munolabeling was observed in multiple areas in the diencephalon, mesen cephalon, pons/medulla, and spinal cord. In the telencephalon, intense labeling was observed in the neuropil throughout layers II-V in the n eocortex, the anterior olfactory nuclear complex, the pyriform cortex, the CA1-CA4 fields and dentate gyrus of the hippocampus, and in many of the septal and basal forebrain areas. In contrast to other members of the opioid receptor family, light labeling for ORL-1 was observed i n telencephalic areas such as caudate-putamen. In the cerebellum, ORL- 1 immunoreactivity was only observed in the deep nuclei. Throughout th e CNS the majority of labelling was localized to fiber processes and f ine puncta, although labeled scattered perikarya were observed in a fe w brain areas such as the hilus dentate in the hippocampus and some nu clei in the brainstem and spinal cord. The present mapping study is co nsistent with the reported distribution of ORL-1 mRNA and provides the first immunohistochemical report on anatomical and cellular distribut ion of ORL-1 receptor in the rat CNS. (C) 1996 Wiley-Liss, Inc.