Food intake elicited by central administration of orexins/hypocretins: identification of hypothalamic sites of action.

Orexin A and B, a recently identified pair of neuropeptides, are produced in perikarya located in the lateral and perifornical hypothalamus (LH and PFH). Immunoreactive fibers from these neurons innervate several nuclei in the hypothalamus. Orexin A and orexin B stimulate feeding when administered intracerebroventricularly to rats. To identify the specific sites of orexin action, orexin A and B were microinjected into a number of hypothalamic and extrahypothalamic sites in rats. Orexin A was found to enhance food intake when injected into four hypothalamic sites, the paraventricular nucleus (PVN), the dorsomedial nucleus (DMN), LH and the perifornical area, but was ineffective in the arcuate nucleus (ARC), the ventromedial nucleus (VMN), and the preoptic area (POA) as well as the central nucleus of the amygdala (CeA) and nucleus of the tractus solitarius (NTS). Orexin B was not effective at any site tested. These findings demonstrate that orexin A receptive sites for stimulation of food intake exist primarily in a narrow band of neural tissue within the hypothalamus that is known to be involved in control of energy homeostasis.