Cannabinoid Receptor Signaling in Central Regulation of Feeding Behavior: A Mini-Review.
Cannabinoid Receptor Signaling in Central Regulation of Feeding Behavior: A Mini-Review.
复制标题
DOI：
10.3389/fnins.2017.00293
复制
发表时间：
2017
影响因子：
4.3
通讯作者：
Koch M
中科院分区：
文献类型：
--
作者：
Koch M
大麻素是调节各种生理过程和改变特定行为产生的脂质信使。在这方面，大麻素受体1型(CB1)是迄今为止最相关的大麻素靶分子。中枢CB1信号的一个主要功能是维持全身能量平衡。因此，大麻素在功能上与控制能量代谢和摄食行为的神经网络中的经典神经递质相互作用。CB1信号的促进可以增加食欲和刺激摄食，而阻断CB1则抑制饥饿和诱导低噬。然而，为了治疗暴饮暴食，反向激动剂利莫那班对CB1的药理阻断不仅抑制了摄食，而且还导致了精神副作用。因此，过去十年的研究集中于破译中枢大麻素信号控制摄食和其他行为的潜在细胞和分子机制，总体目标仍然是确定特定的靶点，以开发安全的药物干预措施治疗肥胖症。今天，许多研究揭开了CB1的亚细胞定位以及大麻在神经元和神经胶质细胞中的功能，这些神经元和神经胶质细胞代表着控制摄食行为的神经回路的组成部分。在这里，将总结这些新的实验发现，并将重点介绍最近在理解CB1依赖的大麻素信号与摄食行为的中枢调节相关的机制方面的进展。最后，将介绍不受CB1激活但也有助于控制取食行为的大麻类化合物的假定替代途径。
Cannabinoids are lipid messengers that modulate a variety of physiological processes and modify the generation of specific behaviors. In this regard, the cannabinoid receptor type 1 (CB1) represents the most relevant target molecule of cannabinoids so far. One main function of central CB1 signaling is to maintain whole body energy homeostasis. Thus, cannabinoids functionally interact with classical neurotransmitters in neural networks that control energy metabolism and feeding behavior. The promotion of CB1 signaling can increase appetite and stimulate feeding, while blockade of CB1 suppresses hunger and induces hypophagia. However, in order to treat overeating, pharmacological blockade of CB1 by the inverse agonist rimonabant not only suppressed feeding but also resulted in psychiatric side effects. Therefore, research within the last decade focused on deciphering the underlying cellular and molecular mechanisms of central cannabinoid signaling that control feeding and other behaviors, with the overall aim still being the identification of specific targets to develop safe pharmacological interventions for the treatment of obesity. Today, many studies unraveled the subcellular localization of CB1 and the function of cannabinoids in neurons and glial cells within circumscribed brain regions that represent integral parts of neural circuitries controlling feeding behavior. Here, these novel experimental findings will be summarized and recent advances in understanding the mechanisms of CB1-dependent cannabinoid signaling being relevant for central regulation of feeding behavior will be highlighted. Finally, presumed alternative pathways of cannabinoids that are not driven by CB1 activation but also contributing to control of feeding behavior will be introduced.