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

TLDR

Orexins are neuropeptides produced by lateral hypothalamic neurons that project widely and influence feeding, sleep, neuroendocrine, and autonomic functions, and although two receptors (OX1R and OX2R) have distinct brain expression patterns, a systematic brain-wide examination had not been reported. The study aimed to systematically map the expression of orexin receptors throughout the rat brain. In situ hybridization histochemistry was used to examine mRNA patterns of both OX1R and OX2R across the brain. OX1R mRNA was found in cortical, hippocampal, thalamic, hypothalamic, raphe, and locus coeruleus regions, whereas OX2R mRNA displayed a complementary distribution in cortical, septal, hippocampal, thalamic, raphe, and multiple hypothalamic nuclei, supporting the notion that differential receptor localization underlies orexin’s diverse physiological roles, including OX2R’s specific contribution to sleep state stability.

Abstract

Orexins (hypocretins) are neuropeptides synthesized in the central nervous system exclusively by neurons of the lateral hypothalamus. Orexin-containing neurons have widespread projections and have been implicated in complex physiological functions including feeding behavior, sleep states, neuroendocrine function, and autonomic control. Two orexin receptors (OX(1)R and OX(2)R) have been identified, with distinct expression patterns throughout the brain, but a systematic examination of orexin receptor expression in the brain has not appeared. We used in situ hybridization histochemistry to examine the patterns of expression of mRNA for both orexin receptors throughout the brain. OX(1)R mRNA was observed in many brain regions including the prefrontal and infralimbic cortex, hippocampus, paraventricular thalamic nucleus, ventromedial hypothalamic nucleus, dorsal raphe nucleus, and locus coeruleus. OX(2)R mRNA was prominent in a complementary distribution including the cerebral cortex, septal nuclei, hippocampus, medial thalamic groups, raphe nuclei, and many hypothalamic nuclei including the tuberomammillary nucleus, dorsomedial nucleus, paraventricular nucleus, and ventral premammillary nucleus. The differential distribution of orexin receptors is consistent with the proposed multifaceted roles of orexin in regulating homeostasis and may explain the unique role of the OX(2)R receptor in regulating sleep state stability.