研究人员以分子和遗传工具为主题，证明细胞内5-羟色胺（血清素）2A受体（5-HT2AR）介导了致幻剂的塑性促进特性；这些结果解释了为什么其他没有参与。这项工作强调了定位偏向在5-HT2AR信号转导中的作用，确定了细胞内5-HT2AR可作为治疗靶点，并提出了一种有趣的可能性，即血清素可能不是皮层中细胞内5-HT2AR的内源性配体。
研究人员表示，皮层树突棘密度的降低是一些神经精神疾病的标志，而促进皮层神经元生长的能力被假设为致幻剂快速而持久的治疗效果的基础。5-HT2AR的激活对于迷幻剂诱导的皮层可塑性至关重要，但目前尚不清楚为什么一些5-HT2AR激动剂促进神经可塑性，而另一些则没有。
附：英文原文
Title: Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors
Author: Maxemiliano V. Vargas, Lee E. Dunlap, Chunyang Dong, Samuel J. Carter, Robert J. Tombari, Shekib A. Jami, Lindsay P. Cameron, Seona D. Patel, Joseph J. Hennessey, Hannah N. Saeger, John D. McCorvy, John A. Gray, Lin Tian, David E. Olson
Issue&Volume: 2023-02-17
Abstract: Decreased dendritic spine density in the cortex is a hallmark of several neuropsychiatric diseases, and the ability to promote cortical neuron growth has been hypothesized to underlie the rapid and sustained therapeutic effects of psychedelics. Activation of 5-hydroxytryptamine (serotonin) 2A receptors (5-HT2ARs) is essential for psychedelic-induced cortical plasticity, but it is currently unclear why some 5-HT2AR agonists promote neuroplasticity, whereas others do not. We used molecular and genetic tools to demonstrate that intracellular 5-HT2ARs mediate the plasticity-promoting properties of psychedelics; these results explain why serotonin does not engage similar plasticity mechanisms. This work emphasizes the role of location bias in 5-HT2AR signaling, identifies intracellular 5-HT2ARs as a therapeutic target, and raises the intriguing possibility that serotonin might not be the endogenous ligand for intracellular 5-HT2ARs in the cortex.
DOI: adf0435
Source: https://www.science.org/doi/10.1126/science.adf0435