title: Addiction-like Synaptic Impairments in Diet-Induced Obesity.
abstract: There is increasing evidence that the pathological overeating underlying some forms of obesity is compulsive in nature and therefore contains elements of an addictive disorder. However, direct physiological evidence linking obesity to synaptic plasticity akin to that occurring in addiction is lacking. We sought to establish whether the propensity to diet-induced obesity (DIO) is associated with addictive-like behavior, as well as synaptic impairments in the nucleus accumbens core considered hallmarks of addiction.
  
  
  
  Sprague Dawley rats were allowed free access to a palatable diet for 8 weeks then separated by weight gain into DIO-prone and DIO-resistant subgroups. Access to palatable food was then restricted to daily operant self-administration sessions using fixed ratio 1, 3, and 5 and progressive ratio schedules. Subsequently, nucleus accumbens brain slices were prepared, and we tested for changes in the ratio between α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartate currents and the ability to exhibit long-term depression.
  
  
  
  We found that propensity to develop DIO is linked to deficits in the ability to induce long-term depression in the nucleus accumbens, as well as increased potentiation at these synapses as measured by AMPA/N-methyl-D-aspartate currents. Consistent with these impairments, we observed addictive-like behavior in DIO-prone rats, including 1) heightened motivation for palatable food; 2) excessive intake; and 3) increased food seeking when food was unavailable.
  
  
  
  Our results show overlap between the propensity for DIO and the synaptic changes associated with facets of addictive behavior, supporting partial coincident neurological underpinnings for compulsive overeating and drug addiction.
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425.|Florey Institute of Neuroscience & Mental Health, University of Melbourne, Parkville, Australia.
authors.forename: Robyn Mary
authors.initials: RM
authors.lastname: Brown
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425.|Department of Medical Neurobiology, The Hebrew University, Jerusalem, Israel.
authors.forename: Yonatan Michael
authors.initials: YM
authors.lastname: Kupchik
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425.
authors.forename: Sade
authors.initials: S
authors.lastname: Spencer
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425.|Departamento de Farmacología, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Constanza
authors.initials: C
authors.lastname: Garcia-Keller
authors.affiliation: Department of Physiology, Monash University, Clayton, Australia.
authors.forename: David C
authors.initials: DC
authors.lastname: Spanswick
authors.affiliation: Florey Institute of Neuroscience & Mental Health, University of Melbourne, Parkville, Australia.
authors.forename: Andrew John
authors.initials: AJ
authors.lastname: Lawrence
authors.affiliation: Department of Physiology, Monash University, Clayton, Australia.
authors.forename: Stephanie Elise
authors.initials: SE
authors.lastname: Simonds
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425.
authors.forename: Danielle Joy
authors.initials: DJ
authors.lastname: Schwartz
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425.
authors.forename: Kelsey Ann
authors.initials: KA
authors.lastname: Jordan
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425.
authors.forename: Thomas Clayton
authors.initials: TC
authors.lastname: Jhou
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425.
authors.forename: Peter William
authors.initials: PW
authors.lastname: Kalivas
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000503:physiopathology*; D003216:Conditioning, Operant / Q000502:physiology; D004032:Diet; D005247:Feeding Behavior; D018698:Glutamic Acid / Q000502:physiology; D036881:Long-Term Synaptic Depression; D008297:Male; D009473:Neuronal Plasticity; D009714:Nucleus Accumbens / Q000502:physiology*; D009765:Obesity / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology
chemical_list: D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid
keywords: Food addiction; Glutamate; Long-term depression; Nucleus accumbens; Obesity; Synaptic plasticity
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