title: Neuropeptide Y activity in the nucleus accumbens modulates feeding behavior and neuronal activity.
abstract: BACKGROUND
  Neuropeptide Y (NPY) is a hypothalamic neuropeptide that plays a prominent role in feeding and energy homeostasis. Expression of the NPY Y1 receptor (Y1R) is highly concentrated in the nucleus accumbens (Acb), a region important in the regulation of palatable feeding. In this study, we performed a number of experiments to investigate the actions of NPY in the Acb.
  
  
  METHODS
  First, we determined caloric intake and food choice after bilateral administration of NPY in the Acb in rats on a free-choice diet of saturated fat, 30% sucrose solution, and standard chow and whether this was mediated by the Y1R. Second, we measured the effect of intra-Acb NPY on neuronal activity using in vivo electrophysiology. Third, we examined co-localization of Y1R with enkephalin and dynorphin neurons and the effect of NPY on preproenkephalin messenger RNA levels in the striatum using fluorescent and radioactive in situ hybridization. Finally, using retrograde tracing, we examined whether NPY neurons in the arcuate nucleus projected to the Acb.
  
  
  RESULTS
  In rats on the free-choice, high-fat, high-sugar diet, intra-Acb NPY increased intake of fat, but not sugar or chow, and this was mediated by the Y1R. Intra-Acb NPY reduced neuronal firing, as well as preproenkephalin messenger RNA expression in the striatum. Moreover, Acb enkephalin neurons expressed Y1R and arcuate nucleus NPY neurons projected to the Acb.
  
  
  CONCLUSIONS
  NPY reduces neuronal firing in the Acb resulting in increased palatable food intake. Together, our neuroanatomical, pharmacologic, and neuronal activity data support a role and mechanism for intra-Acb NPY-induced fat intake.
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Netherlands. Electronic address: j.k.vandenheuvel@amc.uva.nl.
authors.forename: José K
authors.initials: JK
authors.lastname: van den Heuvel
authors.affiliation: Division of Molecular Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Kara
authors.initials: K
authors.lastname: Furman
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Netherlands.
authors.forename: Myrtille C R
authors.initials: MC
authors.lastname: Gumbs
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Netherlands.
authors.forename: Leslie
authors.initials: L
authors.lastname: Eggels
authors.affiliation: Division of Molecular Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Darren M
authors.initials: DM
authors.lastname: Opland
authors.affiliation: Division of Molecular Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Land
authors.affiliation: Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, The Netherlands.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Kolk
authors.affiliation: Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, Iowa.
authors.forename: Nandakumar S
authors.initials: NS
authors.lastname: Narayanan
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Fliers
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Netherlands; Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience, Amsterdam, Netherlands.
authors.forename: Andries
authors.initials: A
authors.lastname: Kalsbeek
authors.affiliation: Division of Molecular Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: DiLeone
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Netherlands.
authors.forename: Susanne E
authors.initials: SE
authors.lastname: la Fleur
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000033:anatomy & histology / Q000502:physiology; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000502:physiology; D004041:Dietary Fats / Q000008:administration & dosage; D019422:Dietary Sucrose / Q000008:administration & dosage; D004399:Dynorphins / Q000378:metabolism; D004435:Eating / Q000187:drug effects / Q000502:physiology; D004745:Enkephalins / Q000378:metabolism; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009478:Neuropeptide Y / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D019422:Dietary Sucrose; D004745:Enkephalins; D009478:Neuropeptide Y; D011498:Protein Precursors; D012333:RNA, Messenger; D017476:Receptors, Neuropeptide Y; D004399:Dynorphins; C033660:preproenkephalin
keywords: Accumbens; Diet; Enkephalin; Feeding; Neuropeptide; Obesity
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