title: Calorie seeking, but not hedonic response, contributes to hyperphagia in a mouse model for Prader-Willi syndrome.
abstract: Prader-Willi syndrome (PWS) is a neurodevelopmental disorder caused by deletion or inactivation of paternally expressed imprinted genes on human chromosome 15q11-q13, the most recognised feature of which is hyperphagia. This is thought to arise as a consequence of abnormalities in both the physiological drive for food and the rewarding properties of food. Although a number of mouse models for PWS exist, the underlying variables dictating maladaptive feeding remain unknown. Here, feeding behaviour in a mouse model in which the imprinting centre (IC) of the syntenic PWS interval has been deleted (PWS(ICdel) mice) is characterised. It is demonstrated that PWS(ICdel) mice show hyperghrelinaemia and increased consumption of food both following overnight fasting and when made more palatable with sucrose. However, hyperphagia in PWS(ICdel) mice was not accompanied by any changes in reactivity to the hedonic properties of palatable food (sucrose or saccharin), as measured by lick-cluster size. Nevertheless, overall consumption by PWS(ICdel) mice for non-caloric saccharin in the licking test was significantly reduced. Combined with converging findings from a continuous reinforcement schedule, these data indicate that PWS(ICdel) mice show a marked heightened sensitivity to the calorific value of food. Overall, these data indicate that any impact of the rewarding properties of food on the hyperphagia seen in PWS(ICdel) mice is driven primarily by calorie content and is unlikely to involve hedonic processes. This has important implications for understanding the neural systems underlying the feeding phenotype of PWS and the contribution of imprinted genes to abnormal feeding behaviour more generally.
authors.affiliation: Behavioural Genetics Group, MRC Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute, Cardiff University, Hadyn Ellis Building, Cardiff, CF24 4HQ, UK.|School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Davies
authors.affiliation: Behavioural Genetics Group, MRC Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute, Cardiff University, Hadyn Ellis Building, Cardiff, CF24 4HQ, UK.|School of Psychology, Cardiff University, Cardiff, UK.
authors.forename: Trevor
authors.initials: T
authors.lastname: Humby
authors.affiliation: School of Psychology, Cardiff University, Cardiff, UK.|School of Psychology, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Dominic M
authors.initials: DM
authors.lastname: Dwyer
authors.affiliation: Centre for Integrative Physiology, University of Edinburgh, Edinburgh, UK.
authors.forename: Alastair S
authors.initials: AS
authors.lastname: Garfield
authors.affiliation: Behavioural Genetics Group, MRC Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute, Cardiff University, Hadyn Ellis Building, Cardiff, CF24 4HQ, UK.|School of Medicine, Cardiff University, Cardiff, UK.|School of Biosciences, Cardiff University, Cardiff, UK.
authors.forename: Hannah
authors.identifier: http://orcid.org/0000-0002-7279-1812
authors.initials: H
authors.lastname: Furby
authors.affiliation: Behavioural Genetics Group, MRC Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute, Cardiff University, Hadyn Ellis Building, Cardiff, CF24 4HQ, UK.|School of Medicine, Cardiff University, Cardiff, UK.|School of Psychology, Cardiff University, Cardiff, UK.
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Wilkinson
authors.affiliation: School of Biosciences, Cardiff University, Cardiff, UK.
authors.forename: Timothy
authors.initials: T
authors.lastname: Wells
authors.affiliation: Behavioural Genetics Group, MRC Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute, Cardiff University, Hadyn Ellis Building, Cardiff, CF24 4HQ, UK.|School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Isles
mesh_terms: D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D057565:Apathy / Q000502:physiology; D003216:Conditioning, Operant; D004195:Disease Models, Animal; D004435:Eating / Q000235:genetics; D002149:Energy Intake / Q000235:genetics / Q000502:physiology*; D005260:Female; D005518:Food Preferences / Q000502:physiology; D054439:Ghrelin / Q000097:blood; D006963:Hyperphagia / Q000209:etiology* / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009042:Motivation / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D011218:Prader-Willi Syndrome / Q000097:blood / Q000150:complications* / Q000235:genetics
chemical_list: D054439:Ghrelin
keywords: Prader-Willi syndrome; hyperphagia; lick-cluster analysis; palatability