Aida Mohammadkhani, Caitlin Mitchell, Morgan H. James, Stephanie L. Borgland, Christopher V. Dayas
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引用次数: 0
摘要
由神经肽奥曲肽-A 和奥曲肽-B 组成的奥曲肽系统(又称视网膜下视素)于 25 年前被发现,并立即被确定为睡眠和觉醒的中枢调节器。这些肽与两种 G 蛋白偶联受体--奥曲肽 1(OX1)和奥曲肽 2(OX2)受体--相互作用,它们能够与所有异三聚 G 蛋白亚家族偶联,但主要传递钙信号的增加。促肾上腺皮质激素神经元受多种递质系统和环境刺激(包括食物和药物相关线索)的调控,而环境刺激则是奖励可用性的信号。奥列克辛神经元也会被预期、压力、预测动机相关信息的线索(包括预测滥用药物的线索)激活,并调动神经调节系统(包括腹侧被盖区(VTA)的多巴胺神经元)对这些信号做出反应。因此,奥曲肽神经元被描述为动机激活因子,可协调包括进食和唤醒在内的一系列功能,使个体能够对动机相关信息做出反应,这对生存至关重要。这篇综述重点探讨了矿肽在食欲动机中的作用,并强调了这些神经肽在动机唤醒水平过高(暴饮暴食、焦虑症和药物使用障碍)与动机受损(抑郁症)的病症中的作用。
Contribution of hypothalamic orexin (hypocretin) circuits to pathologies of motivation
The orexin (also known as hypocretin) system, consisting of neuropeptides orexin-A and orexin-B, was discovered over 25 years ago and was immediately identified as a central regulator of sleep and wakefulness. These peptides interact with two G-protein coupled receptors, orexin 1 (OX1) and orexin 2 (OX2) receptors which are capable of coupling to all heterotrimeric G-protein subfamilies, but primarily transduce increases in calcium signalling. Orexin neurons are regulated by a variety of transmitter systems and environmental stimuli that signal reward availability, including food and drug related cues. Orexin neurons are also activated by anticipation, stress, cues predicting motivationally relevant information, including those predicting drugs of abuse, and engage neuromodulatory systems, including dopamine neurons of the ventral tegmental area (VTA) to respond to these signals. As such, orexin neurons have been characterized as motivational activators that coordinate a range of functions, including feeding and arousal, that allow the individual to respond to motivationally relevant information, critical for survival. This review focuses on the role of orexins in appetitive motivation and highlights a role for these neuropeptides in pathologies characterized by inappropriately high levels of motivated arousal (overeating, anxiety and substance use disorders) versus those in which motivation is impaired (depression).
期刊介绍:
The British Journal of Pharmacology (BJP) is a biomedical science journal offering comprehensive international coverage of experimental and translational pharmacology. It publishes original research, authoritative reviews, mini reviews, systematic reviews, meta-analyses, databases, letters to the Editor, and commentaries.
Review articles, databases, systematic reviews, and meta-analyses are typically commissioned, but unsolicited contributions are also considered, either as standalone papers or part of themed issues.
In addition to basic science research, BJP features translational pharmacology research, including proof-of-concept and early mechanistic studies in humans. While it generally does not publish first-in-man phase I studies or phase IIb, III, or IV studies, exceptions may be made under certain circumstances, particularly if results are combined with preclinical studies.