Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats.
Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats.
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DOI：
10.1038/nn.2519
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发表时间：
2010-05
影响因子：
25
通讯作者：
Kenny PJ
中科院分区：
文献类型：
--
作者：
Johnson PM;Kenny PJ
我们发现肥胖的发展伴随着大脑奖励缺陷的逐渐恶化。可卡因或海洛因引起的奖赏稳态的类似变化被认为是从偶然到强迫性吸毒转变的关键触发因素。因此，我们在肥胖大鼠中检测到了强迫性进食行为，但在瘦大鼠中没有检测到。纹状体多巴胺D2受体（D2R）在肥胖大鼠中下调，类似于人类药物成瘾者的先前报告。此外，慢病毒介导的纹状体D2R的敲除迅速加速了成瘾样奖励缺陷的发展和大鼠在长期获得美味高脂肪食物的情况下出现强迫性食物寻求。这些数据表明，过度食用可口的食物会触发大脑奖赏回路中的成瘾样神经适应性反应，并推动强迫性进食的发展。因此，共同的享乐机制可能是肥胖和药物成瘾的基础。
We found that development of obesity was coupled with the emergence of a progressively worsening brain reward deficit. Similar changes in reward homeostasis induced by cocaine or heroin is considered a critical trigger in 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 (D2R) were downregulated in obese rats, similar to previous reports in human drug addicts. Moreover, lentivirus-mediated knockdown of striatal D2R 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 circuitries and drives the development of compulsive eating. Common hedonic mechanisms may therefore underlie obesity and drug addiction.
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