title: GHS-R1a signaling in the DMH and VMH contributes to food anticipatory activity.
abstract: BACKGROUND
  Rats that have restricted access to food at a fixed time point of the circadian phase display high levels of food anticipatory activity (FAA). The orexigenic hormone ghrelin has been implicated in the regulation of FAA. However, it is not known via which brain area ghrelin exerts this effect. Growth hormone secretagogue receptor 1a (GHS-R1a) is highly expressed in the hypothalamus, including the dorsomedial hypothalamus (DMH) and the ventromedial hypothalamus (VMH). These two hypothalamic areas have been reported to play a role in FAA.
  
  
  OBJECTIVE
  To examine the role of GHS-R1a signaling in the DMH and VMH in FAA.
  
  
  METHODS
  Adeno-associated virus expressing a shRNA directed against GHS-R1a was used to establish local knockdown of GHS-R1a in the DMH and VMH in rats. Rats were subsequently subjected to a restricted feeding schedule (RFS).
  
  
  RESULTS
  Under ad libitum conditions, knockdown of GHS-R1a in the VMH increased food intake and body weight gain. In addition, GHS-R1a knockdown in VMH and DMH reduced body temperature and running wheel activity (RWA). When rats were subjected to a RFS, the main effect of GHS-R1a knockdown in both DMH and VMH was a decrease in RWA and an attenuation of body weight loss. Rats with knockdown of GHS-R1a in DMH and VMH showed a delay in onset of FAA. In addition, GHS-R1a knockdown in DMH resulted in a reduction of FAA amplitude.
  
  
  CONCLUSIONS
  This is the first study to investigate the effect of local hypothalamic knockdown of GHS-R1a on FAA. Our results implicate hypothalamic GHS-R1a signaling in the regulation of FAA. Nevertheless, some FAA remained, suggesting that a distributed network of brain areas and signaling pathways is involved in the development of FAA.
authors.affiliation: Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Merkestein
authors.affiliation: Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: van Gestel
authors.affiliation: Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: E M
authors.initials: EM
authors.lastname: van der Zwaal
authors.affiliation: Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: Brans
authors.affiliation: Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: M C
authors.initials: MC
authors.lastname: Luijendijk
authors.affiliation: Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: A J
authors.initials: AJ
authors.lastname: van Rozen
authors.affiliation: Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Hendriks
authors.affiliation: Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: K M
authors.initials: KM
authors.lastname: Garner
authors.affiliation: Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: A J
authors.initials: AJ
authors.lastname: Boender
authors.affiliation: Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Pandit
authors.affiliation: Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Adan
mesh_terms: D000818:Animals; D001831:Body Temperature; D001835:Body Weight; D004435:Eating; D005247:Feeding Behavior; D054439:Ghrelin / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D054440:Receptors, Ghrelin / Q000378:metabolism*; D015398:Signal Transduction; D015430:Weight Gain
chemical_list: D054439:Ghrelin; D054440:Receptors, Ghrelin