title: Diet-induced obesity: dopamine transporter function, impulsivity and motivation.
abstract: OBJECTIVE
  A rat model of diet-induced obesity (DIO) was used to determine dopamine transporter (DAT) function, impulsivity and motivation as neurobehavioral outcomes and predictors of obesity.
  
  
  METHODS
  To evaluate neurobehavioral alterations following the development of DIO induced by an 8-week high-fat diet (HF) exposure, striatal D2-receptor density, DAT function and expression, extracellular dopamine concentrations, impulsivity, and motivation for high- and low-fat reinforcers were determined. To determine predictors of DIO, neurobehavioral antecedents including impulsivity, motivation for high-fat reinforcers, DAT function and extracellular dopamine were evaluated before the 8-week HF exposure.
  
  
  METHODS
  Striatal D2-receptor density was determined by in vitro kinetic analysis of [(3)H]raclopride binding. DAT function was determined using in vitro kinetic analysis of [(3)H]dopamine uptake, methamphetamine-evoked [(3)H]dopamine overflow and no-net flux in vivo microdialysis. DAT cell-surface expression was determined using biotinylation and western blotting. Impulsivity and food-motivated behavior were determined using a delay discounting task and progressive ratio schedule, respectively.
  
  
  RESULTS
  Relative to obesity-resistant (OR) rats, obesity-prone (OP) rats exhibited 18% greater body weight following an 8-week HF-diet exposure, 42% lower striatal D2-receptor density, 30% lower total DAT expression, 40% lower in vitro and in vivo DAT function, 45% greater extracellular dopamine and twofold greater methamphetamine-evoked [(3)H]dopamine overflow. OP rats exhibited higher motivation for food, and surprisingly, were less impulsive relative to OR rats. Impulsivity, in vivo DAT function and extracellular dopamine concentration did not predict DIO. Importantly, motivation for high-fat reinforcers predicted the development of DIO.
  
  
  CONCLUSIONS
  Human studies are limited by their ability to determine if impulsivity, motivation and DAT function are causes or consequences of DIO. The current animal model shows that motivation for high-fat food, but not impulsive behavior, predicts the development of obesity, whereas decreases in striatal DAT function are exhibited only after the development of obesity.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: V
authors.initials: V
authors.lastname: Narayanaswami
authors.forename: A C
authors.initials: AC
authors.lastname: Thompson
authors.forename: L A
authors.initials: LA
authors.lastname: Cassis
authors.forename: M T
authors.initials: MT
authors.lastname: Bardo
authors.forename: L P
authors.initials: LP
authors.lastname: Dwoskin
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001835:Body Weight; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005247:Feeding Behavior; D007175:Impulsive Behavior; D008297:Male; D009042:Motivation; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012201:Reward; D015398:Signal Transduction
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D017448:Receptors, Dopamine D2; D004298:Dopamine