title: Orexin signaling in the ventral tegmental area is required for high-fat appetite induced by opioid stimulation of the nucleus accumbens.
abstract: The overriding of satiety and homeostatic control mechanisms by cognitive, rewarding, and emotional aspects of palatable foods may contribute to the evolving obesity crisis, but little is known about neural pathways and mechanisms responsible for crosstalk between the "cognitive" and "metabolic" brain in the control of appetite. Here we show that neural connections between the nucleus accumbens and hypothalamus might be part of this link. Using the well known model of selective stimulation of high-fat intake induced by intra-accumbens injection of the mu-opioid receptor agonist D-Ala2-N-Me-Phe4-gly5-ol-enkephalin (DAMGO), we demonstrate that orexin signaling in the ventral tegmental area is important for this reward-driven appetite to override metabolic repletion signals in presatiated rats. We further show that accumbens DAMGO in the absence of food selectively increases the proportion of orexin neurons expressing c-Fos in parts of the perifornical hypothalamus and that neural projections originating in DAMGO-responsive sites of the nucleus accumbens make close anatomical contacts with hypothalamic orexin neurons. These findings suggest that direct accumbens-hypothalamic projections can stimulate hypothalamic orexin neurons, which in turn through orexin-1 receptor signaling in the ventral tegmental area and possibly other sites interfaces with the motivational and motor systems to increase intake of palatable food.
authors.affiliation: Neurobiology of Nutrition Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana 70808, USA.
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Zheng
authors.forename: Laurel M
authors.initials: LM
authors.lastname: Patterson
authors.forename: Hans-Rudolf
authors.initials: HR
authors.lastname: Berthoud
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D001066:Appetite / Q000187:drug effects / Q000502:physiology*; D001069:Appetite Regulation / Q000187:drug effects / Q000502:physiology; D004041:Dietary Fats; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000008:administration & dosage; D047908:Intracellular Signaling Peptides and Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D064446:Orexin Receptors; D000068797:Orexins; D051381:Rats; D017207:Rats, Sprague-Dawley; D018013:Receptors, Neuropeptide / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology*
chemical_list: D000701:Analgesics, Opioid; D004041:Dietary Fats; C497459:Hcrtr1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D018013:Receptors, Neuropeptide; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-