Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats

Abstract

Overeating can be compulsive, resembling drug addiction. This paper reports that in rats, developing diet-induced obesity correlates with decreasing sensitivity of the brain's reward system. Knockdown of the striatal dopamine receptor D2 led to rapid loss of reward function and to compulsive overeating undeterred by conditioned aversive foot shocks. 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.