Molecular and Behavioral Neuroscience Laboratory, Department of Pharmacology, Universidade Federal de São Paulo (UNIFESP), São Paulo, São Paulo, Brazil; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, United States.
Molecular and Behavioral Neuroscience Laboratory, Department of Pharmacology, Universidade Federal de São Paulo (UNIFESP), São Paulo, São Paulo, Brazil.
Int Rev Neurobiol. 2024;178:355-381. doi: 10.1016/bs.irn.2024.08.004. Epub 2024 Oct 24.
Over the decades, preclinical models have been developed and refined to investigate the rewarding effects of addictive substances and the neurobiological underpinnings of alcohol and other drug use disorders. This chapter delves into the methodological foundations, advantages, and limitations of leading animal models used to study alcohol use disorders (AUDs). Some models focus on the early stages of alcohol use and abuse. For instance, conditioned place preference assesses associative learning between a specific context and the effects of the drug, while locomotor sensitization measures increased locomotor activity following repeated drug exposure. In contrast, contingent models such as operant and non-operant alcohol self-administration protocols gauge voluntary intake, preference, motivation, and seeking behavior for alcohol solutions among experimental subjects. Additionally, we discuss the chronic intermittent alcohol vapor model, extensively utilized to induce a phenotype resembling dependence through non-contingent inhalation of alcohol vapor, resulting in elevated blood alcohol concentrations. Given the focus on pharmacological treatments for AUDs, we explore how different animal models can be employed to evaluate potential therapies and extrapolate findings to alcohol-related behaviors in humans. This chapter aims to provide readers with a comprehensive understanding of various animal models for AUDs, aiding in the interpretation of preclinical studies and the selection of suitable models for future research endeavors.
几十年来,已经开发和完善了临床前模型,以研究成瘾物质的奖励作用以及酒精和其他药物使用障碍的神经生物学基础。本章深入探讨了用于研究酒精使用障碍(AUD)的主要动物模型的方法学基础、优点和局限性。一些模型侧重于酒精使用和滥用的早期阶段。例如,条件位置偏好评估特定环境与药物作用之间的联想学习,而运动敏化则衡量重复药物暴露后运动活动的增加。相比之下,操作性和非操作性酒精自我给药方案等条件模型衡量实验对象对酒精溶液的自愿摄入、偏好、动机和寻求行为。此外,我们还讨论了慢性间歇性酒精蒸气模型,该模型通过非条件吸入酒精蒸气广泛用于诱导类似于依赖的表型,导致血液酒精浓度升高。鉴于重点是酒精使用障碍的药物治疗,我们探讨了如何使用不同的动物模型来评估潜在的治疗方法,并将研究结果推断到人类的酒精相关行为。本章旨在为读者提供对 AUD 各种动物模型的全面了解,有助于解释临床前研究并为未来的研究工作选择合适的模型。