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非人灵长类动物的脑成像:对药物成瘾的见解

Brain imaging in nonhuman primates: insights into drug addiction.

作者信息

Nader Michael A, Czoty Paul W

机构信息

Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.

出版信息

ILAR J. 2008;49(1):89-102. doi: 10.1093/ilar.49.1.89.

Abstract

In vivo brain imaging enables the systematic examination of trait and state variables that contribute to the etiology of human diseases. This review highlights the use of in vivo imaging in nonhuman primate models of drug abuse. In efforts to translate findings from laboratory animals to humans, monkey models offer considerable advantages over those that use rodents and other species because of their neurobiological similarity to humans and their longer life span, which makes it possible to study individual subjects over several years. This article provides a brief overview of positron emission tomography (PET), magnetic resonance imaging (MRI)-based techniques, and encephalographic approaches, with a focus on methodological issues that investigators new to the field should consider. We discuss PET imaging studies involving the dopamine (DA) system, with a special emphasis on DA D2 receptors, and describe experimental approaches through which PET imaging data can provide information about the neuropharmacological and neurochemical actions of drugs that modify behavior. We also consider the use of imaging to understand the impact and interactions of genetic predispositions and environmental and physiological modulators on disease states. For MRI-based and encephalographic studies, we describe approaches that can provide new information about brain function. Although much work remains to be done to adapt and apply these techniques for routine use in nonhuman primates, there has been much progress. These techniques will provide the foundation for future studies aimed at developing behavioral and pharmacological treatments for many human diseases.

摘要

体内脑成像能够系统地检查导致人类疾病病因的特质和状态变量。本综述重点介绍了体内成像在药物滥用非人灵长类动物模型中的应用。为了将实验室动物的研究结果转化到人类身上,猴子模型相对于使用啮齿动物和其他物种的模型具有相当大的优势,因为它们在神经生物学上与人类相似,且寿命更长,这使得对个体受试者进行数年的研究成为可能。本文简要概述了正电子发射断层扫描(PET)、基于磁共振成像(MRI)的技术和脑电描记法,重点关注该领域新研究人员应考虑的方法学问题。我们讨论了涉及多巴胺(DA)系统的PET成像研究,特别强调DA D2受体,并描述了PET成像数据可提供有关改变行为的药物的神经药理学和神经化学作用信息的实验方法。我们还考虑了利用成像来理解遗传易感性以及环境和生理调节因素对疾病状态的影响和相互作用。对于基于MRI和脑电描记法的研究,我们描述了能够提供有关脑功能新信息的方法。尽管要将这些技术应用于非人灵长类动物的常规研究还有很多工作要做,但已经取得了很大进展。这些技术将为未来旨在开发针对多种人类疾病的行为和药物治疗方法的研究奠定基础。

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