Developmental Trajectories of Anhedonia in Preclinical Models.
Developmental Trajectories of Anhedonia in Preclinical Models.
复制标题
DOI：
10.1007/7854_2021_299
复制
发表时间：
2022
影响因子：
--
通讯作者：
Baram, Tallie Z
中科院分区：
文献类型：
--
作者：
Birnie, Matthew T;Levis, Sophia C;Mahler, Stephen V;Baram, Tallie Z
本章讨论如何在临床前模型中操作和研究快感缺失的复杂概念。它提供了有关快感缺乏症在早期生活逆境中发展的信息，以及临床前模型梳理出导致快感缺乏症样行为的不同分子、表观遗传和网络机制的力量。具体地说，我们首先讨论了快感缺乏一词，回顾了与奖励相关的行为背后的概念成分，并区分了快感缺乏与动机行为和消耗性行为的缺陷。然后，我们描述了临床前模型中用于研究快感缺乏症类行为的实验方法的曲目，以及在过去十年中对实验工具(例如，化学遗传学、光遗传学)和概念结构(显着性、价态、冲突)的逐步完善。接下来，我们将概述执行快乐性行为的不同方面的大脑回路、节点和投射的当前知识状态，以及参与产生快乐性行为的神经递质、调节器和受体。最后，我们讨论了早年逆境后出现的快感缺乏症的特殊情况，作为一个雄辩的例子，使我们能够研究快感缺乏症的因果关系、机制和性别依赖。总之，本章强调了使用临床前模型的力量、潜力和局限性，以促进我们对快感缺失的起源和机制的理解，并发现其预防和缓解的潜在靶点。
This chapter discusses how the complex concept of anhedonia can be operationalized and studied in preclinical models. It provides information about the development of anhedonia in the context of early life adversity, and the power of preclinical models to tease out the diverse molecular, epigenetic and network mechanisms that are responsible for anhedonia-like behaviors. Specifically, we first discuss the term anhedonia, reviewing the conceptual components underlying reward-related behaviors and distinguish anhedonia pertaining to deficits in motivational versus consummatory behaviors. We then describe the repertoire of experimental approaches employed to study anhedonia-like behaviors in preclinical models, and the progressive refinement over the past decade of both experimental instruments (e.g., chemogenetics, optogenetics) and conceptual constructs (salience, valence, conflict). We follow with an overview of the state of current knowledge of brain circuits, nodes and projections that execute distinct aspects of hedonic-like behaviors, as well as neurotransmitters, modulators and receptors involved in the generation of anhedonia-like behaviors. Finally, we discuss the special case of anhedonia that arises following early-life adversity as an eloquent example enabling the study of causality, mechanisms and sex dependence of anhedonia. Together, this chapter highlights the power, potential and limitations of using pre-clinical models to advance our understanding of the origin and mechanisms of anhedonia and to discover potential targets for its prevention and mitigation.