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强迫症动物模型:最新研究发现与未来方向

Animal models of obsessive compulsive disorder: recent findings and future directions.

机构信息

Centro de Investigación en Reproducción Animal , Universidad Autónoma de Tlaxcala - CINVESTAV, Tlaxcala , México , 90000

出版信息

Expert Opin Drug Discov. 2011 Jul;6(7):725-37. doi: 10.1517/17460441.2011.577772. Epub 2011 Jun 2.

Abstract

INTRODUCTION

Obsessive compulsive disorder (OCD) is a debilitating condition with limited treatment options. OCD is heterogeneous with respect to the content of obsessions and compulsions and their underlying motivation, among other characteristics. Animal models have provided important insights into the pathophysiology of OCD.

AREAS COVERED

The phenomenology of OCD is discussed, with emphasis on clinically-relevant subgroups. The paper also discusses the advantages and limitations of animals as models of OCD, along with considerations on assessing their validity. A PubMed database search using the terms 'animal model' and 'obsessive compulsive disorder' revealed ongoing studies in several models, including stereotypy in the deer mouse, quinpirole-induced checking, spontaneous alternation, compulsive lever pressing, genetic models, pathogenic models and models involving normal compulsive-like behavioral patterns. These models are presented with respect to their similarity to specific features of OCD and the information gained from them. Studies in many of these models point to the participation of corticostriatal thalamocortical circuitry and corticostriatal glutamate neurotransmission in the pathophysiology of compulsive-like behavior.

EXPERT OPINION

The use of animal models takes us beyond simple serotonin- or dopamine-based models of OCD that are founded on the often limited, and still unexplained, response of OCD symptoms to serotonin reuptake inhibitors or antipsychotic therapy. Pharmacological challenges that selectively target neurochemical systems that modulate either corticostriatal glutamate or striatal dopamine neurotransmission, or indeed both, should be investigated in animal models of compulsive-like behavior. Such systems include metabotropic glutamate, adenosine and endocannabinoid receptors, among others.

摘要

简介

强迫症(OCD)是一种使人衰弱的疾病,治疗选择有限。OCD 在强迫观念和强迫行为的内容及其潜在动机等方面存在异质性。动物模型为 OCD 的病理生理学提供了重要的见解。

涵盖领域

讨论了 OCD 的现象学,重点是具有临床相关性的亚组。本文还讨论了动物作为 OCD 模型的优缺点,以及评估其有效性的注意事项。使用术语“动物模型”和“强迫症”对 PubMed 数据库进行搜索,揭示了几种模型中的正在进行的研究,包括鹿鼠刻板行为、喹吡罗诱导的检查、自发交替、强迫按压杠杆、遗传模型、致病模型和涉及正常强迫样行为模式的模型。这些模型根据它们与 OCD 的特定特征的相似性以及从中获得的信息进行呈现。这些模型中的许多研究表明,皮质纹状体丘脑皮质回路和皮质纹状体谷氨酸能神经传递参与了强迫样行为的病理生理学。

专家意见

动物模型的使用使我们超越了基于简单的 5-羟色胺或多巴胺的 OCD 模型,这些模型基于 OCD 症状对 5-羟色胺再摄取抑制剂或抗精神病药物治疗的反应往往有限,并且仍未得到解释。应该在强迫样行为的动物模型中研究选择性靶向调节皮质纹状体谷氨酸或纹状多巴胺神经传递的神经化学系统,或者实际上是两者的药理学挑战。此类系统包括代谢型谷氨酸、腺苷和内源性大麻素受体等。

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