Orexin (ORX)-A and -B are recently identified neuropeptides, which are spec
ifically localized in neurons within and around the lateral hypothalamic ar
ea (LHA) and dorsomedial hypothalamic nucleus (DMH), the regions classicall
y implicated in feeding behavior. Here, we report a further study of the di
stribution of ORX-containing neurons in the adult rat brain to provide a ge
neral overview of the ORX neuronal system. Immunohistochemical study using
anti-ORX antiserum showed ORX-immunoreactive (ir) neurons specifically loca
lized within the hypothalamus, including the perifornical nucleus, LHA, DMH
, and posterior hypothalamic area. ORX-ir axons and their varicose terminal
s showed a widespread distribution throughout the adult rat brain. ORX-ir n
erve terminals were observed throughout the hypothalamus, including the arc
uate nucleus and paraventricular hypothalamic nucleus, regions implicated i
n the regulation of feeding behavior. We also observed strong staining of O
RX-ir varicose terminals in areas outside the hypothalamus, including the c
erebral cortex, medial groups of the thalamus, circumventricular organs (su
bfornical organ and area postrema), Limbic system (hippocampus, amygdala, a
nd indusium griseum), and brain stem (locus coeruleus and raphe nuclei). Th
ese results indicate that the ORX system provides a link between the hypoth
alamus and other brain regions, and that ORX-containing LHA and DMH neurons
play important roles in integrating the complex physiology underlying feed
ing behavior. (C) 1999 Elsevier Science B.V. All rights reserved.