title: Ventral tegmental area orexin 1 receptors promote palatable food intake and oppose postingestive negative feedback.
abstract: Hypothalamic orexin neurons project to numerous brain areas, including the ventral tegmental area (VTA), which is involved in motivation and food-seeking behavior. Here we address how exogenously administered orexin-A and endogenous orexin 1 receptor (OX1R) activation in the VTA affects feeding behavior. We hypothesized that orexin-A and OX1R antagonist SB334867 delivered to the VTA, at doses that were subthreshold for effect when injected into the ventricle, would affect intake of palatable foods in multiple test situations. We first used a hedonic feeding model in which satiated rats selectively consume a high-fat diet (HFD). Intra-VTA orexin-A stimulated additional consumption of chow and increased HFD intake in this model. In ad libitum-fed rats given daily 30-min test sessions, intra-VTA orexin-A also increased intake of HFD and 0.1 M sucrose. Further analysis of licking patterns revealed that that VTA orexin-A increased meal size and licking burst size only toward the end of the meal. Consistent with this finding, a subthreshold dose of VTA orexin-A prevented intake suppression induced by gastrointestinal nutrient infusion. Surprisingly, intra-VTA orexin-A had no effect on operant responding for sucrose pellets on a progressive ratio schedule of reinforcement. A role for endogenous VTA OX1R stimulation is supported by our finding that bilateral VTA injection of the selective OX1R antagonist SB334867 suppressed 0.1 M sucrose intake. Together, our data suggest that OX1R activity in the VTA facilitates food intake, potentially by counteracting postingestive negative feedback that would normally suppress feeding later in a meal.
authors.affiliation: Department of Psychology & Program in Neuroscience, Florida State University, Tallahassee, Florida; and.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Terrill
authors.affiliation: Department of Psychology & Program in Neuroscience, Florida State University, Tallahassee, Florida; and.
authors.forename: Kellie M
authors.initials: KM
authors.lastname: Hyde
authors.affiliation: Department of Psychology & Program in Neuroscience, Florida State University, Tallahassee, Florida; and.
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Kay
authors.affiliation: Department of Psychology & Program in Neuroscience, Florida State University, Tallahassee, Florida; and.
authors.forename: Hayden E
authors.initials: HE
authors.lastname: Greene
authors.affiliation: Department of Psychology & Program in Neuroscience, Florida State University, Tallahassee, Florida; and.
authors.forename: Calyn B
authors.initials: CB
authors.lastname: Maske
authors.affiliation: Department of Psychology & Program in Neuroscience, Florida State University, Tallahassee, Florida; and.
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Knierim
authors.affiliation: Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, Washington.
authors.forename: Jon F
authors.initials: JF
authors.lastname: Davis
authors.affiliation: Department of Psychology & Program in Neuroscience, Florida State University, Tallahassee, Florida; and williams@psy.fsu.edu.
authors.forename: Diana L
authors.identifier: 0000-0002-3548-7440
authors.initials: DL
authors.lastname: Williams
mesh_terms: D000818:Animals; D001069:Appetite Regulation / Q000502:physiology*; D004435:Eating / Q000502:physiology*; D025461:Feedback, Physiological / Q000502:physiology*; D008297:Male; D009042:Motivation / Q000502:physiology; D064446:Orexin Receptors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D017557:Ventral Tegmental Area / Q000502:physiology*
chemical_list: C578627:Hcrtr1 protein, rat; D064446:Orexin Receptors
keywords: food intake; orexin 1 receptors; orexin-A; palatable foods; ventral tegmental area