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啮齿动物和灵长类动物中催产素和加压素受体研究的比较视角:转化意义

Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications.

作者信息

Freeman Sara M, Young Larry J

机构信息

Department of Psychology, California National Primate Research Center, University of California-Davis, Davis, CA, USA.

Department of Psychiatry and Behavioral Sciences, Silvio O. Conte Center for Oxytocin and Social Cognition, Center for Translational Social Neuroscience, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.

出版信息

J Neuroendocrinol. 2016 Apr;28(4). doi: 10.1111/jne.12382.

Abstract

In the last several decades, sophisticated experimental techniques have been used to determine the neurobiology of the oxytocin and vasopressin systems in rodents. Using a suite of methodologies, including electrophysiology, site-specific selective pharmacology, receptor autoradiography, in vivo microdialysis, and genetic and optogenetic manipulations, we have gained unprecedented knowledge about how these neuropeptides engage neural circuits to regulate behaviour, particularly social behaviour. Based on this foundation of information from rodent studies, we have started generating new hypotheses and frameworks about how the oxytocin and vasopressin systems could be acting in humans to influence social cognition. However, despite the recent inundation of publications using intranasal oxytocin in humans, we still know very little about the neurophysiology of the oxytocin system in primates more broadly. Furthermore, the design and analysis of these human studies have remained largely uninformed of the potential neurobiological mechanisms underlying their findings. Although the methods available for studying the oxytocin and vasopressin systems in humans are incredibly limited as a result of practical and ethical considerations, there is great potential to fill the gaps in our knowledge by developing better nonhuman primate models of social functioning. Behavioural pharmacology and receptor autoradiography have been used to study the oxytocin and vasopressin systems in nonhuman primates, and there is now great potential to broaden our understanding of the neurobiology of these systems. In this review, we discuss comparative findings in receptor distributions in rodents and primates, with perspectives on the functionality of conserved regions of expression in these distinct mammalian clades. We also identify specific ways that established technologies can be used to answer basic research questions in primates. Finally, we highlight areas of future research in nonhuman primates that are experimentally poised to yield critical insights into the anatomy, physiology and behavioural effects of the oxytocin system, given its remarkable translational potential.

摘要

在过去几十年中,先进的实验技术已被用于确定啮齿动物中催产素和加压素系统的神经生物学。通过一系列方法,包括电生理学、位点特异性选择性药理学、受体放射自显影、体内微透析以及基因和光遗传学操作,我们对这些神经肽如何参与神经回路以调节行为,特别是社会行为,有了前所未有的认识。基于啮齿动物研究的这一信息基础,我们开始提出关于催产素和加压素系统如何在人类中发挥作用以影响社会认知的新假设和框架。然而,尽管最近有大量关于人类使用鼻内催产素的出版物,但我们对更广泛的灵长类动物中催产素系统的神经生理学仍然知之甚少。此外,这些人类研究的设计和分析在很大程度上仍未考虑其发现背后潜在的神经生物学机制。由于实际和伦理方面的考虑,可用于研究人类催产素和加压素系统的方法极其有限,但通过开发更好的社会功能非人类灵长类动物模型,填补我们知识空白的潜力巨大。行为药理学和受体放射自显影已被用于研究非人类灵长类动物中的催产素和加压素系统,现在有很大潜力拓宽我们对这些系统神经生物学的理解。在这篇综述中,我们讨论了啮齿动物和灵长类动物受体分布的比较结果,并对这些不同哺乳动物类群中保守表达区域的功能进行了展望。我们还确定了现有技术可用于回答灵长类动物基础研究问题的具体方式。最后,鉴于催产素系统具有显著的转化潜力,我们强调了非人类灵长类动物未来研究的领域,这些研究有望在实验上对催产素系统的解剖学、生理学和行为效应产生关键见解。

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