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.
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.
Striatal D2-receptor density was determined by in vitro kinetic analysis of [3H]raclopride binding. DAT function was determined using in vitro kinetic analysis of [3H]dopamine uptake, methamphetamine-evoked [3H]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.
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 [3H]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.
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.
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Lost in Translation? On the Need for Convergence in Animal and Human Studies on the Role of Dopamine in Diet-Induced Obesity
Current Addiction Reports Open Access 08 August 2019
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We acknowledge Agripina Deaciuc, Andrew Smith, Andrew Chip Meyer, David Lee, Deann Hopkins, Emily Denehy, Gurpreet Dhawan, Kate Fischer, Kiran Babu Siripurapu, Travis McCuddy and Victoria English for help with the assays. We thank Dr Robert Lorch for help with the statistical analyses. This research was supported by NIH P50 DA05312 (Linda P Dwoskin), NIH HL73085 and P20RR021954 (Lisa A Cassis) and a Pre-doctoral Fellowship from the American Heart Association, AHA 715489B (Vidya Narayanaswami).
The authors declare no conflict of interest.
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Narayanaswami, V., Thompson, A., Cassis, L. et al. Diet-induced obesity: dopamine transporter function, impulsivity and motivation. Int J Obes 37, 1095–1103 (2013). https://doi.org/10.1038/ijo.2012.178
- diet-induced obesity
- dopamine transporter
A limited and intermittent access to a high-fat diet modulates the effects of cocaine-induced reinstatement in the conditioned place preference in male and female mice
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