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强迫症动物模型综述:聚焦于发育、免疫、内分泌及行为模型

A review of animal models of obsessive-compulsive disorder: a focus on developmental, immune, endocrine and behavioral models.

作者信息

Grados Marco, Prazak Michael, Saif Aneeqa, Halls Andrew

机构信息

a Department of Psychiatry , Johns Hopkins University , 1800 Orleans St. - 12th floor, Baltimore , MD 21287 , USA.

b Department of Medicine , Dow University of Health Sciences , Karachi , Pakistan.

出版信息

Expert Opin Drug Discov. 2016;11(1):27-43. doi: 10.1517/17460441.2016.1103225. Epub 2015 Nov 11.

Abstract

INTRODUCTION

Obsessive-compulsive disorder (OCD) is a neuropsychiatric condition characterized by intrusive thoughts (obsessions) and/or repetitive behaviors (compulsions). Several models of OCD exist, many which employ behaviors such as over-grooming or hoarding as correlates for compulsive behaviors - often using a response to serotonergic agents as evidence for their validity. Recent discoveries in the genetics of OCD and the identification of aberrancies of glutamatergic, hormonal, and immune pathways in the OCD phenotype highlight a need to review existing of animal models of OCD. The focus of attention to these pathways may lead to possible new targets for drug discovery.

AREAS COVERED

In this review, the authors describe frameworks for animal models in OCD conceptualized as either biological (e.g., developmental, genetic, and endocrine pathways), or behavioral (e.g., repetitive grooming, and stereotypies). In addition, the authors give special attention to the emerging role of glutamate in OCD.

EXPERT OPINION

While many animal models for OCD demonstrate pathologic repetitive behavior phenotypes, which are relieved by serotoninergic agents, animal models based on reversal learning, perseverative responding, and neurodevelopmental mechanisms represent robust new paradigms. Glutamatergic influences in these new animal models suggest that drug discovery using neuroprotective approaches may represent a new stage for pharmacologic developments in OCD.

摘要

引言

强迫症(OCD)是一种神经精神疾病,其特征为侵入性思维(强迫观念)和/或重复行为(强迫行为)。存在多种强迫症模型,其中许多采用过度梳理毛发或囤积等行为作为强迫行为的相关因素——通常将对血清素能药物的反应作为其有效性的证据。强迫症遗传学的最新发现以及强迫症表型中谷氨酸能、激素和免疫途径异常的识别凸显了回顾现有强迫症动物模型的必要性。关注这些途径可能会为药物研发带来新的靶点。

涵盖领域

在本综述中,作者描述了强迫症动物模型的框架,这些模型被概念化为生物学模型(例如,发育、遗传和内分泌途径)或行为学模型(例如,重复梳理毛发和刻板行为)。此外,作者特别关注谷氨酸在强迫症中日益凸显的作用。

专家观点

虽然许多强迫症动物模型表现出病理性重复行为表型,且血清素能药物可缓解这些表型,但基于逆向学习、持续性反应和神经发育机制的动物模型代表了强大的新范式。这些新动物模型中的谷氨酸能影响表明,使用神经保护方法进行药物研发可能代表了强迫症药物开发的新阶段。

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