Transient and sustained effects of dopamine and serotonin signaling in motivation‐related behavior
Transient and sustained effects of dopamine and serotonin signaling in motivation‐related behavior
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DOI：
10.1111/pcn.12942
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发表时间：
2019-10
影响因子：
11.9
通讯作者：
Sho Yagishita
中科院分区：
文献类型：
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作者：
Sho Yagishita
对抗抑郁药和非典型抗精神病药物的药理学研究表明，多巴胺和5-羟色胺信号在抑郁症中起着作用。然而，仅仅基于全脑范围内这些分子浓度的降低或增加，很难解释抑郁症状和治疗效果。最近使用先进的神经元操纵和观察技术进行的动物研究揭示了详细的多巴胺和5-羟色胺动力学，它们调节与动机相关的行为的不同方面。多巴胺和5-羟色胺在从亚秒到分钟的时间尺度上短暂地调节每一时刻的行为，并产生持续的影响，如与奖励相关的学习和持续数天以上的压力反应。暂时性和持续性效应通常根据投射部位的不同而表现出特定的作用，在这些部位，需要不同的突触和细胞机制来处理每个瞬时和持续性时间尺度的神经递质。因此，与动机相关的行为的特定方面似乎受到特定脑区不同突触和细胞机制的调节，这些机制是多巴胺和5-羟色胺信号短暂和持续影响的基础。最近的临床研究表明，有抑郁症状的受试者表现出短暂和持续的信号功能受损；此外，他们在抑郁症状和神经元功能障碍方面表现出异质性。抑郁症状可以通过每个短暂和持续的信号机制的功能障碍来解释，而相关机制中不同的损害模式可能解释了症状的异质性。因此，对多巴胺和5-羟色胺信号的详细了解可能会为抑郁症状提供新的见解。
Pharmacological studies of antidepressants and atypical antipsychotics have suggested a role of dopamine and serotonin signaling in depression. However, depressive symptoms and treatment effects are difficult to explain based simply on brain‐wide decrease or increase in the concentrations of these molecules. Recent animal studies using advanced neuronal manipulation and observation techniques have revealed detailed dopamine and serotonin dynamics that regulate diverse aspects of motivation‐related behavior. Dopamine and serotonin transiently modulate moment‐to‐moment behavior at timescales ranging from sub‐second to minutes and also produce persistent effects, such as reward‐related learning and stress responses that last longer than several days. Transient and sustained effects often exhibit specific roles depending on the projection sites, where distinct synaptic and cellular mechanisms are required to process the neurotransmitters for each transient and sustained timescale. Therefore, it appears that specific aspects of motivation‐related behavior are regulated by distinct synaptic and cellular mechanisms in specific brain regions that underlie the transient and sustained effects of dopamine and serotonin signaling. Recent clinical studies have implied that subjects with depressive symptoms show impaired transient and sustained signaling functions; moreover, they exhibit heterogeneity in depressive symptoms and neuronal dysfunction. Depressive symptoms may be explained by the dysfunction of each transient and sustained signaling mechanism, and distinct patterns of impairment in the relevant mechanisms may explain the heterogeneity of symptoms. Thus, detailed understanding of dopamine and serotonin signaling may provide new insight into depressive symptoms.