Abstract:
The serotonergic system is involved in diverse cognitive functions including memory. Of particular importance to daily life are declarative memories that contain information about personal experiences, general facts, and events. Several psychiatric or neurological diseases, such as depression, attention-deficit-hyperactivity disorder (ADHD), and dementia, show alterations in serotonergic signalling and attendant memory disorders. Nevertheless, understanding serotonergic neurotransmission and its influence on memory remained a challenge until today. In this systematic review, we summarize recent psychopharmacological studies in animals and humans from a psychological memory perspective, in consideration of task-specific requirements. This approach has the advantage that comparisons between serotonin (5-HT)-related neurochemical mechanisms and manipulations are each addressing specific mnemonic circuits. We conclude that applications of the same 5-HT-related treatments can differentially affect unrelated tasks of declarative memories. Moreover, the analysis of specific mnemonic phases (e.g., encoding vs. consolidation) reveals opposing impacts of increased or decreased 5-HT tones, with low 5-HT supporting spatial encoding but impairing the consolidation of objects and verbal memories. Promising targets for protein synthesis-dependent consolidation enhancements include 5-HT4 receptor agonists and 5-HT6 receptor antagonists, with the latter being of special interest for the treatment of age-related decline. Further implications are pointed out as base for the development of novel therapeutic targets for memory impairment of neuropsychiatric disorders.
摘要:
5-羟色胺能系统参与包括记忆在内的多种认知功能。对日常生活特别重要的是陈述性记忆,其中包含有关个人经历的信息,一般事实,和事件。几种精神或神经疾病,比如抑郁症,注意缺陷多动障碍(ADHD),和痴呆症,显示血清素能信号的改变和伴随的记忆障碍。然而,直到今天,理解5-羟色胺能神经传递及其对记忆的影响仍然是一个挑战。在这次系统审查中,我们从心理记忆的角度总结了最近在动物和人类的心理药理学研究,考虑到特定任务的要求。这种方法的优点在于,与5-羟色胺(5-HT)相关的神经化学机制和操作之间的比较均针对特定的记忆回路。我们得出的结论是,相同的5-HT相关治疗方法的应用可以不同地影响陈述性记忆的无关任务。此外,特定记忆阶段的分析(例如,编码vs.合并)揭示了增加或减少5-HT音调的相反影响,低5-HT支持空间编码,但损害对象和言语记忆的巩固。蛋白质合成依赖性巩固增强的有希望的靶标包括5-HT4受体激动剂和5-HT6受体拮抗剂,后者对与年龄相关的下降的治疗特别感兴趣。指出了进一步的意义,作为开发神经精神疾病记忆障碍的新型治疗靶标的基础。