Department of Neurobiology, The University of Chicago Chicago, IL, USA.
Front Integr Neurosci. 2012 Jul 20;6:49. doi: 10.3389/fnint.2012.00049. eCollection 2012.
Accumulating evidence indicates integration of dopamine function with metabolic signals, highlighting a potential role for dopamine in energy balance, frequently construed as modulating reward in response to homeostatic state. Though its precise role remains controversial, the reward perspective of dopamine has dominated investigation of motivational disorders, including obesity. In the hypothesis outlined here, we suggest instead that the primary role of dopamine in behavior is to modulate activity to adapt behavioral energy expenditure to the prevailing environmental energy conditions, with the role of dopamine in reward and motivated behaviors derived from its primary role in energy balance. Dopamine has long been known to modulate activity, exemplified by psychostimulants that act via dopamine. More recently, there has been nascent investigation into the role of dopamine in modulating voluntary activity, with some investigators suggesting that dopamine may serve as a final common pathway that couples energy sensing to regulated voluntary energy expenditure. We suggest that interposed between input from both the internal and external world, dopamine modulates behavioral energy expenditure along two axes: a conserve-expend axis that regulates generalized activity and an explore-exploit axes that regulates the degree to which reward value biases the distribution of activity. In this view, increased dopamine does not promote consumption of tasty food. Instead increased dopamine promotes energy expenditure and exploration while decreased dopamine favors energy conservation and exploitation. This hypothesis provides a mechanistic interpretation to an apparent paradox: the well-established role of dopamine in food seeking and the findings that low dopaminergic functions are associated with obesity. Our hypothesis provides an alternative perspective on the role of dopamine in obesity and reinterprets the "reward deficiency hypothesis" as a perceived energy deficit. We propose that dopamine, by facilitating energy expenditure, should be protective against obesity. We suggest the apparent failure of this protective mechanism in Western societies with high prevalence of obesity arises as a consequence of sedentary lifestyles that thwart energy expenditure.
越来越多的证据表明多巴胺功能与代谢信号的整合，突显了多巴胺在能量平衡中的潜在作用，通常被认为是调节奖励以响应体内平衡状态。尽管其确切作用仍存在争议，但多巴胺的奖励观点主导了动机障碍的研究，包括肥胖症。在本文概述的假设中，我们建议多巴胺在行为中的主要作用是调节活动，使行为能量消耗适应当前的环境能量条件，而多巴胺在奖励和动机行为中的作用则源自其在能量平衡中的主要作用。多巴胺长期以来一直被认为可以调节活动，例如通过多巴胺起作用的精神兴奋剂。最近，人们对多巴胺在调节自愿活动中的作用进行了初步研究，一些研究人员认为，多巴胺可能是一种将能量感应与调节性自愿能量消耗联系起来的最终共同途径。我们建议，在内部和外部世界的输入之间，多巴胺沿着两个轴调节行为能量消耗：一个是调节一般活动的保存-消耗轴，另一个是调节奖励价值对活动分布的偏向程度的探索-利用轴。在这种观点下，多巴胺的增加并不会促进美味食物的消耗。相反，多巴胺的增加会促进能量消耗和探索，而多巴胺的减少则有利于能量的保存和利用。这个假设为一个明显的悖论提供了一个机械解释：多巴胺在食物寻找中的既定作用，以及低多巴胺功能与肥胖有关的发现。我们的假设为多巴胺在肥胖中的作用提供了另一种视角，并将“奖励缺乏假说”重新解释为感知的能量不足。我们提出，多巴胺通过促进能量消耗，应该对肥胖有保护作用。我们建议，在肥胖症高发的西方社会中，这种保护机制的明显失效是由于久坐不动的生活方式阻碍了能量消耗所致。
