Laboratory of Behavioral and Molecular Neuroscience, Department of Molecular Therapeutics, The Scripps Research Institute-Scripps Florida, Jupiter, Florida, USA.
Nat Neurosci. 2010 May;13(5):635-41. doi: 10.1038/nn.2519. Epub 2010 Mar 28.
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.
我们发现，肥胖的发展伴随着神经奖励反应逐渐恶化的缺陷的出现。可卡因或海洛因引起的类似的奖励平衡变化被认为是触发从偶然到强迫性药物使用的转变的关键因素。因此，我们在肥胖但不瘦的大鼠中检测到类似于强迫的进食行为，这表现为对厌恶条件刺激的破坏有抵抗力的美味食物的消耗。纹状体多巴胺 D2 受体 (D2R) 在肥胖大鼠中下调，正如在对药物上瘾的人类中所报道的那样。此外，纹状体 D2R 的慢病毒介导的敲低迅速加速了类似成瘾的奖励缺陷的发展，并在延长获得美味高脂肪食物的大鼠中引发了类似强迫的食物寻找。这些数据表明，美味食物的过度摄入会引发大脑奖励回路中类似成瘾的神经适应性反应，并导致强迫性进食的发展。因此，共同的享乐机制可能是肥胖和药物成瘾的基础。
