The Rise and Fall of Dopamine: A Two-Stage Model of the Development and Entrenchment of Anorexia Nervosa.
The Rise and Fall of Dopamine: A Two-Stage Model of the Development and Entrenchment of Anorexia Nervosa.
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DOI：
10.3389/fpsyt.2021.799548
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发表时间：
2021
影响因子：
4.7
通讯作者：
Burghardt NS
中科院分区：
文献类型：
--
作者：
Beeler JA;Burghardt NS
多巴胺长期以来被认为是介导神经性厌食症（AN）的关键神经底物。尽管有近50年的研究，多巴胺功能变化的假定方向仍然不清楚，多巴胺在AN中的机制作用尚未达成共识。我们假设AN有两个阶段--对应于初始发展和巩固--其特征是多巴胺的相反变化。首先，热量限制，特别是当与运动相结合时，会引发多巴胺的螺旋式上升，促进建立和加强减肥行为所必需的行为可塑性。第二，慢性自我饥饿逆转这种升级，以减少或损害多巴胺，这反过来又赋予行为的稳定性和巩固现在建立的AN行为。这种多巴胺增强，随后受损的模式可能是许多行为障碍的共同途径，其特征是强化学习和随后的行为不稳定性。如果正确，我们的假设对AN和其他疾病（如成瘾和肥胖）具有重要的临床和研究意义。
Dopamine has long been implicated as a critical neural substrate mediating anorexia nervosa (AN). Despite nearly 50 years of research, the putative direction of change in dopamine function remains unclear and no consensus on the mechanistic role of dopamine in AN has been achieved. We hypothesize two stages in AN– corresponding to initial development and entrenchment– characterized by opposite changes in dopamine. First, caloric restriction, particularly when combined with exercise, triggers an escalating spiral of increasing dopamine that facilitates the behavioral plasticity necessary to establish and reinforce weight-loss behaviors. Second, chronic self-starvation reverses this escalation to reduce or impair dopamine which, in turn, confers behavioral inflexibility and entrenchment of now established AN behaviors. This pattern of enhanced, followed by impaired dopamine might be a common path to many behavioral disorders characterized by reinforcement learning and subsequent behavioral inflexibility. If correct, our hypothesis has significant clinical and research implications for AN and other disorders, such as addiction and obesity.
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DOI：
10.1038/s41386-020-00799-1
发表时间：
2020-11
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
Augustin SM;Loewinger GC;O'Neal TJ;Kravitz AV;Lovinger DM
通讯作者：
Lovinger DM
影响因子：
3.5
作者：
Beeler JA;Frazier CR;Zhuang X
通讯作者：
Zhuang X
影响因子：
11.3
作者：
Broft A;Slifstein M;Osborne J;Kothari P;Morim S;Shingleton R;Kenney L;Vallabhajosula S;Attia E;Martinez D;Timothy Walsh B
通讯作者：
Timothy Walsh B
影响因子：
3.8
作者：
Casper, Regina C.
通讯作者：
Casper, Regina C.
影响因子：
16.2
作者：
Borgland, SL;Taha, SA;Bonci, A
通讯作者：
Bonci, A