Addiction-like reward dysfunction and compulsive eating in obese rats: Role for dopamine D2 receptors

By Paul M Johnson, P. Kenny. Nature Neuroscience, 2010

1,410 citations recorded by the source corpus.

We found that development of obesity was coupled with emergence of a progressively worsening deficit in neural reward responses. Similar changes in reward homeostasis induced by cocaine or heroin are considered to be crucial in triggering the transition from casual to compulsive drug-taking. Accordingly, we detected compulsive-like feeding behavior in obese but not lean rats, measured as palatable food consumption that was resistant to disruption by an aversive conditioned stimulus. Striatal dopamine D2 receptors (D2Rs) were downregulated in obese rats, as has been reported in humans addicted to drugs. Moreover, lentivirus-mediated knockdown of striatal D2Rs rapidly accelerated the development of addiction-like reward deficits and the onset of compulsive-like food seeking in rats with extended access to palatable high-fat food. These data demonstrate that overconsumption of palatable food triggers addiction-like neuroadaptive responses in brain reward circuits and drives the development of compulsive eating. Common hedonic mechanisms may therefore underlie obesity and drug addiction.

Subfields: Cellular and Molecular Neuroscience, Clinical Psychology, Endocrine and Autonomic Systems

View Paper: https://www.semanticscholar.org/paper/260dea6d0146905a34404a3e6ca7014753da951e

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

In Clinical Psychology

In Endocrine and Autonomic Systems

Citations in the corpus

Reward Mechanisms in Obesity: New Insights and Future Directions (2011, methodology): “Similar to the downregulated striatal D2R levels in obese human subjects, D2R levels are also lowered inmice and rats fed a palatable diet (e.g., Colantuoni et al., 2001; Geiger et al., 2009; Johnson and Kenny, 2010) and in rats genetically predisposed to obesity (Zucker rats) (Thanos et al., 2008).”
Which Foods May Be Addictive? The Roles of Processing, Fat Content, and Glycemic Load (2015, background): “Rats maintained on a diet of highly processed foods, such as cheesecake, exhibit downregulation in the dopamine system that also occurs in response to drugs of abuse [30].”
Cafeteria Diet Is a Robust Model of Human Metabolic Syndrome With Liver and Adipose Inflammation: Comparison to High-Fat Diet (2011, background): “engages hedonic feeding, consistent with the observed voluntary hyperphagia, which produces long-lasting neuronal alterations predicted to underlie non-homeostatically regulated feeding behaviors associated with some forms of human obesity (11,12).”
Reward, dopamine and the control of food intake: implications for obesity (2010, neutral): “Importantly, decreases in striatal D2R have been linked to compulsive food intake in obese rodents [59] and with decreased metabolic activity in OFC and ACC in obese humans [60] (Figure 3a–c).”
fMRI Reactivity to High-Calorie Food Pictures Predicts Short- and Long-Term Outcome in a Weight-Loss Program (2012, background): “…-PA Author M anuscript N IH -PA Author M anuscript N IH -PA Author M anuscript accumulating that overconsumption and weight gain can blunt the activation of reward areas by food (Colantuoni et al., 2001; Johnson and Kenny, 2010; Stice et al., 2010b; Val-Laillet et al., 2011; Wilcox et al., 2010).”