Serotonin and brain function: a tale of two receptors.
Serotonin and brain function: a tale of two receptors.
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DOI：
10.1177/0269881117725915
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发表时间：
2017-09
期刊：
影响因子：
--
通讯作者：
Nutt DJ
中科院分区：
文献类型：
--
作者：
Carhart-Harris RL;Nutt DJ
以前试图确定大脑5-羟色胺功能的统一理论在很大程度上未能达成共识。在本合成中，我们将以前的观点与新的和旧的数据相结合，以创建一个新的二分模型为中心，认为5-羟色胺神经传递增强了两种不同的适应性反应逆境，在很大程度上介导的两个最普遍和研究的大脑受体：5-HT 1A和5-HT 2A受体。我们建议，被动应对（即容忍的压力源）介导的突触后5-HT 1AR信号转导和压力缓和的特点。相反，我们认为，积极应对（即积极解决压力源）是由5-HT 2AR信号转导介导的，其特征是可塑性增强（定义为改变的能力）。我们认为，5-HT 1AR介导的压力调节可能是大脑对逆境的默认反应，但通过5-HT 2AR介导的可塑性改变一个人的处境和/或与它的关系的能力也可能很重要-随着逆境水平达到临界点，这种能力也越来越重要。我们认为，5-HT 1AR途径是增强传统的5-HT再摄取阻断抗抑郁药，如选择性5-羟色胺再摄取抑制剂（SSRIs），而5-HT 2AR途径是增强5-HT 2AR激动剂致幻剂。这种二分模型旨在解释不同的药物（SSRIs和致幻剂）如何以不同的方式调节多巴胺能系统，可以实现互补的适应性和潜在的治疗效果。
Previous attempts to identify a unified theory of brain serotonin function have largely failed to achieve consensus. In this present synthesis, we integrate previous perspectives with new and older data to create a novel bipartite model centred on the view that serotonin neurotransmission enhances two distinct adaptive responses to adversity, mediated in large part by its two most prevalent and researched brain receptors: the 5-HT1A and 5-HT2A receptors. We propose that passive coping (i.e. tolerating a source of stress) is mediated by postsynaptic 5-HT1AR signalling and characterised by stress moderation. Conversely, we argue that active coping (i.e. actively addressing a source of stress) is mediated by 5-HT2AR signalling and characterised by enhanced plasticity (defined as capacity for change). We propose that 5-HT1AR-mediated stress moderation may be the brain’s default response to adversity but that an improved ability to change one’s situation and/or relationship to it via 5-HT2AR-mediated plasticity may also be important – and increasingly so as the level of adversity reaches a critical point. We propose that the 5-HT1AR pathway is enhanced by conventional 5-HT reuptake blocking antidepressants such as the selective serotonin reuptake inhibitors (SSRIs), whereas the 5-HT2AR pathway is enhanced by 5-HT2AR-agonist psychedelics. This bipartite model purports to explain how different drugs (SSRIs and psychedelics) that modulate the serotonergic system in different ways, can achieve complementary adaptive and potentially therapeutic outcomes.
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影响因子：
2.9
作者：
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