title: Orexin-A enhances feeding in male rats by activating hindbrain catecholamine neurons.
abstract: Both lateral hypothalamic orexinergic neurons and hindbrain catecholaminergic neurons contribute to control of feeding behavior. Orexin fibers and terminals are present in close proximity to hindbrain catecholaminergic neurons, and fourth ventricular (4V) orexin injections that increase food intake also increase c-Fos expression in hindbrain catecholamine neurons, suggesting that orexin neurons may stimulate feeding by activating catecholamine neurons. Here we examine that hypothesis in more detail. We found that 4V injection of orexin-A (0.5 nmol/rat) produced widespread activation of c-Fos in hindbrain catecholamine cell groups. In the A1 and C1 cell groups in the ventrolateral medulla, where most c-Fos-positive neurons were also dopamine β hydroxylase (DBH) positive, direct injections of a lower dose (67 pmol/200 nl) of orexin-A also increased food intake in intact rats. Then, with the use of the retrogradely transported immunotoxin, anti-DBH conjugated to saporin (DSAP), which targets and destroys DBH-expressing catecholamine neurons, we examined the hypothesis that catecholamine neurons are required for orexin-induced feeding. Rats given paraventricular hypothalamic injections of DSAP, or unconjugated saporin (SAP) as control, were implanted with 4V or lateral ventricular (LV) cannulas and tested for feeding in response to ventricular injection of orexin-A (0.5 nmol/rat). Both LV and 4V orexin-A stimulated feeding in SAP controls, but DSAP abolished these responses. These results reveal for the first time that catecholamine neurons are required for feeding induced by injection of orexin-A into either LV or 4V.
authors.affiliation: Programs in Neuroscience, Washington State University, Pullman, Washington aijunli@vetmed.wsu.edu.
authors.forename: Ai-Jun
authors.identifier: http://orcid.org/0000-0003-3585-886X
authors.initials: AJ
authors.lastname: Li
authors.affiliation: Programs in Neuroscience, Washington State University, Pullman, Washington.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Programs in Neuroscience, Washington State University, Pullman, Washington.
authors.forename: Hana
authors.initials: H
authors.lastname: Davis
authors.affiliation: Programs in Neuroscience, Washington State University, Pullman, Washington.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Programs in Neuroscience, Washington State University, Pullman, Washington.
authors.forename: Sue
authors.initials: S
authors.lastname: Ritter
mesh_terms: D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D002552:Cerebral Ventricles / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004299:Dopamine beta-Hydroxylase / Q000276:immunology / Q000378:metabolism; D004435:Eating / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects*; D000922:Immunotoxins / Q000008:administration & dosage; D007276:Injections, Intraventricular; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage*; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D009479:Neuropeptides / Q000008:administration & dosage*; D000068797:Orexins; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012249:Rhombencephalon / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D054789:Ribosome Inactivating Proteins, Type 1 / Q000008:administration & dosage; D000076985:Saporins
chemical_list: D002395:Catecholamines; D000922:Immunotoxins; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D016760:Proto-Oncogene Proteins c-fos; D054789:Ribosome Inactivating Proteins, Type 1; D004299:Dopamine beta-Hydroxylase; D000076985:Saporins
keywords: catecholamine neurons; feeding; hypocretin; orexin; ventrolateral medulla