啮齿类动物药物成瘾模型的构建方法和应用进展

doi:10.12300/j.issn.1674-5817.2024.080

实验动物与比较医学 ›› 2025, Vol. 45 ›› Issue (2): 158-166.DOI: 10.12300/j.issn.1674-5817.2024.080

啮齿类动物药物成瘾模型的构建方法和应用进展

王碧莹¹^,², 鲁家铄³, 昝桂影³, 陈若松³, 柴景蕊³, 刘景根⁴(), 王瑜珺¹^,²^,³()

^1.烟台大学药学院, 烟台 264000
^2.烟台新药创制山东省实验室, 中科环渤海(烟台)药物高等研究院, 烟台 264117
^3.中国科学院上海药物研究所, 上海 200120
^4.浙江中医药大学, 杭州 310000

收稿日期:2024-06-03 修回日期:2025-02-06 出版日期:2025-04-25 发布日期:2025-04-25
通讯作者: 刘景根（1958—），男，博士，研究员，博士生导师，研究方向：神经精神药理。E-mail： jgliu@simm.ac.cn。ORCID： 0000-0002-2869-0029；
王瑜珺（1981—），女，博士，研究员，博士生导师，研究方向：神经精神药理。E-mail： yjwang@simm.ac.cn。ORCID： 0009-0001-9056-
作者简介:王碧莹（2000—），女，硕士研究生，研究方向：神经精神药理。E-mail： 18993138153@163.com
基金资助:
山东省重点研发计划“重大神经精神疾病关键机制解析及干预新策略研究”(2024CXPT029)

Establishment Methods and Application Progress of Rodent Models for Drug Addiction

WANG Biying¹^,², LU Jiashuo³, ZAN Guiying³, CHEN Ruosong³, CHAI Jingrui³, LIU Jinggen⁴(), WANG Yujun¹^,²^,³()

^1.School of Pharmacy, Yantai University, Yantai 264000, China
^2.Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai 264117, China
^3.Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200120, China
^4.Zhejiang Chinese Medical University, Hangzhou 310000, China

Received:2024-06-03 Revised:2025-02-06 Published:2025-04-25 Online:2025-04-25
Contact: LIU Jinggen (ORCID: 0000-0002-2869-0029), E-mail: jgliu@simm.ac.cn;
WANG Yujun (ORCID: 0009-0001-9056-9692), E-mail: yjwang@simm.ac.cn;

摘要/Abstract

摘要：

药物成瘾也被称为药物依赖或物质使用障碍，是一种慢性复发性脑疾病，其主要特征为强迫性地寻求和使用药物以及失去对用药的控制能力。长期摄入成瘾物质会导致生理和心理上的依赖，一旦停止使用，患者便会经历一系列强烈的不适反应，如焦虑、失眠、恶心、呕吐等，同时还会产生对药物的强烈渴求。药物依赖分为躯体依赖和精神依赖。躯体依赖也被称为生理依赖，是指因反复使用成瘾性药物而导致的病理性适应状态，其在停药后会产生严重的躯体症状，即戒断综合征。精神依赖也被称作心理依赖，是指使用者对成瘾性药物在心理层面的渴求，以获取服药后的特殊快感，并需要定期或持续使用以维持这种欣快感。成瘾机制复杂，受到遗传、环境等多种因素的影响，并涉及记忆、奖赏和决策等高级神经活动。目前在药物成瘾领域仍缺乏有效的治疗手段。面对复杂的成瘾问题，实验动物研究是不可或缺的。合理运用动物行为模型来模拟人类药物成瘾的情况，可以促进对成瘾机制和脑科学奥秘的深入探索与研究。本文以啮齿类动物为主，介绍了与躯体依赖和精神依赖相关的多种动物实验模型，包括躯体依赖模型、行为敏化模型、条件性位置偏爱模型、药物辨别模型和自身给药模型的构建原理、方法和流程，同时对比各实验模型的特点，论述相关模型在揭示成瘾机制方面的适用条件，旨在为成瘾机制的研究和治疗手段的开发提供支持。

关键词: 药物成瘾, 啮齿类, 动物模型, 躯体依赖, 精神依赖

Abstract:

Drug addiction, also referred to as drug dependence or substance use disorder, is a chronic and recurrent brain disease. Its main characteristics are compulsive drug-seeking behavior, continued use of drugs, and a loss of control over intake. Prolonged use of addictive substances can result in both physiological and psychological dependence. When usage is ceased, individuals may experience intense discomfort, including anxiety, insomnia, nausea, vomiting, and a strong craving for the substances. Drug dependence is classified into two types: physical dependence and psychological dependence. Physical dependence describes a pathological state of adaptation that results from the repeated use of addictive substances, leading to severe withdrawal syndrome upon cessation. Psychological dependence involves a mental craving for addictive substances, which is needed to experience the specific euphoria that follows consumption. Regular or continuous use is required to sustain these euphoric effects. The mechanisms of addiction are complex and influenced by genetic, environmental, and various other factors. They involve higher-level neurological activities, such as memory, reward, and decision-making. Currently, effective treatment methods for drug addiction are insufficient. Due to the complexity of drug addiction, laboratory animal research is essential. Using animal behavioral models to simulate human drug addiction can enhance our understanding of the mechanisms of addiction. This research offers a comprehensive overview of various animal experimental models that explore both physical and psychological dependence. It includes detailed descriptions of the methods and procedures used to assess physical dependence, behavioral sensitization, conditioned place preference, drug discrimination, and self-administration experiments. Additionally, the characteristics of each experimental model are compared, and the relevance of these models is discussed, aiming to provide support for the research on addiction mechanisms and the development of therapeutic methods.

Key words: Drug addiction, Rodents, Animal model, Physical dependence, Psychological dependence

中图分类号:

R-332

王碧莹,鲁家铄,昝桂影,等. 啮齿类动物药物成瘾模型的构建方法和应用进展[J]. 实验动物与比较医学, 2025, 45(2): 158-166. DOI: 10.12300/j.issn.1674-5817.2024.080.

WANG Biying,LU Jiashuo,ZAN Guiying,et al. Establishment Methods and Application Progress of Rodent Models for Drug Addiction[J]. Laboratory Animal and Comparative Medicine, 2025, 45(2): 158-166. DOI: 10.12300/j.issn.1674-5817.2024.080.

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啮齿类动物药物成瘾模型的构建方法和应用进展

Establishment Methods and Application Progress of Rodent Models for Drug Addiction

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