中国科学院心理健康重点实验室知识库

动机行为受生理需求相关神经环路的调控， 包括管理摄食、能量代谢等内在动机行为的下丘脑黑皮质素(melanocortin， MC)系统和负责奖赏环路的中脑多巴胺(dopamine， DA)系统. MC系统中前阿黑皮素原(proopiomelanocortin， POMC)神经元与刺豚鼠相关蛋白(agouti-related protein， AgRP)神经元合成与分泌的递质及神经肽协同完成了对摄食等动机行为的调控， 且DA系统通过调节奖赏环路参与摄食等动机行为的发生过程. 此外， 高强度的激活DA系统是成瘾性药物的共同特征， 当DA系统激活与用药行为反复关联后， 部分使用者进入药物成瘾状态， 他们表现出强迫性的觅药动机. 根据已有研究报告提示， 药物成瘾的过程可能是药物导致动机行为调控中枢发生适应性改变的过程， 这个变化反之促发了强迫性觅药行为的形成. 本文将从下丘脑黑皮质素系统两种主要的神经元——POMC神经元和AgRP神经元——在对于摄食和用药相关的奖赏行为调控作用入手， 分析它们与DA系统的相互作用模式， 论述下丘脑黑皮质素系统的功能失调与药物成瘾的关系.

Eating, drinking and taking addictive drugs are the behaviors driven by motivation. They are regulated by neural networks such as the mammalian central melanocortin (MC) system and mesolimbic dopamine (DA) system. The MC system is referred as a collection of central nervous system (CNS) circuits, that include the neurons expressing proopiomelanocortin (POMC) or agouti gene-related protein (AgRP) locating in the arcuate nucleus, the brainstem POMC neurons originating in the commissural nucleus of the solitary tract, and the downstream targets of the POMC and AgRP neurons expressing the melanocortin receptors (MCRs). In the CNS, melanocortin peptides synthetized by POMC neurons are the agonists of the MCRs, while AgRP from AgRP neurons is a high-affinity antagonist to those receptors. The MC system plays a crucial role in regulating body energy homeostasis and multiple processes, such as food intake and reward-associated behaviors, through a certain pattern of cooperation between the POMC and AgRP neurons. The ventral tegmental area (VTA) is another key brain area in modulating reward-associated behaviors. There is a clearly anatomical association between the MC system and the VTA region, that the POMC and AgRP neurons in the ARC have direct projections on the DA neurons in the VTA. Thus, clear presentation of how the POMC and AgRP neurons and the DA system mutually mediate rewarding-associated behaviors may contribute to better understanding some abnormal reward-taking behaviors, such as drug addiction. The previous studies have shown that DA system is a common target for different addictive drugs, direct or indirect, as well as both acute and chronic drug exposure can alter the function of the POMC and AgRP neurons. Additive humans and animals show uncontrollably drug-taking behavior, being analogue to the individuals taking food under a hunger condition. Here, we hypothesize that drug addiction may result from the dysfunction the MC system (especially POMC and AgRP neurons). In other words, the functional balance between the MC and DA systems is disrupted by addictive drugs. This review will firstly summarize how the MC and DA systems collectively govern feeding behavior, and then present what changes happen in the MC system following the drug use, as well as raise the potential mechanism underlying altered function of the MC system after repeated hyperactivation of DA pathway by addictive drugs.

国家重点基础研究发展计划(2015CB553501);; 中国科学院心理健康重点实验室(中国科学院心理研究所)资助项目