Differential expression of orexin receptors 1 and 2 in the rat brain

Orexins (hypocretins) are neuropeptides synthesized in the central nervous system exclusively by neurons of the lateral hypothalamus. Orexin-containin g neurons have widespread projections and have been implicated in complex p hysiological functions including feeding behavior, sleep states, neuroendoc rine function, and autonomic control. Two orexin receptors (OX,R and OX,R) have been identified, with distinct expression patterns throughout the brai n, but a systematic examination of orexin receptor expression in the brain has not appeared. We used in situ hybridization histochemistry to examine t he patterns of expression of mRNA for both orexin receptors throughout the brain. OX,R mRNA was observed in many brain regions including the prefronta l and infralimbic cortex, hippocampus, paraventricular thalamic nucleus, ve ntromedial hypothalamic nucleus, dorsal raphe nucleus, and locus coeruleus. OX,R mRNA was prominent in a complementary distribution including the cere bral cortex, septal nuclei, hippocampus, medial thalamic groups, raphe nucl ei, and many hypothalamic nuclei including the tuberomammillary nucleus, do rsomedial nucleus, paraventricular nucleus, and ventral premammillary nucle us. The differential distribution of orexin receptors is consistent with th e proposed multifaceted roles of orexin in regulating homeostasis and may e xplain the unique role of the OX,R receptor in regulating sleep state stabi lity. (C) 2001 Wiley-Liss, Inc.