High-dose ondansetron reduces activation of interoceptive and sensorimotor brain regions.
High-dose ondansetron reduces activation of interoceptive and sensorimotor brain regions.
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高剂量昂丹司琼可减少内感受和感觉运动大脑区域的激活。
DOI：
10.1038/s41386-018-0174-x
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Goodman,WayneK
中科院分区：
文献类型：
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作者：
Stern,EmilyR;Shahab,Rebbia;Grimaldi,StephanieJ;Leibu,Evan;Murrough,JamesW;Fleysher,Lazar;Parides,MichaelK;Coffey,BarbaraJ;Burdick,KatherineE;Goodman,WayneK
几种精神疾病涉及内感受异常和以小脑为中心的相关神经回路。干预措施的发展调节内感受回路可能会导致这些疾病的新的治疗方法。5-HT 3受体拮抗剂昂丹司琼是一个很好的候选人的调制的内感受性电路，因为5-HT 3受体位于丰富的感觉通路和昂丹司琼已显示出一些临床实用性的障碍，其特征在于感觉和内感受性异常。本研究测试了三种不同剂量的昂丹司琼参与内感受的神经区域的能力，以确定该药物作为治疗药物的效用，以靶向患者的回路异常。53名健康受试者在MRI扫描前分别随机接受8 mg（n= 18）、16 mg（n= 17）或24 mg（n= 18）剂量的昂丹司琼和安慰剂。受试者进行了一项功能磁共振成像任务，先前显示参与内感受电路，他们观看了描述身体运动/感觉和控制视频的视频。结果显示，剂量和激活之间的高度显着的关系，在双边小脑，体感和运动前区，扣带皮层，颞叶皮层控制，但不是身体为重点的视频。这些效应是由24 mg组与安慰剂组相比昂丹司琼的激活显著减少所驱动的，16 mg和8 mg组的效应较弱。总之，高剂量昂丹司琼减少激活的几个领域的重要内感受，包括脑皮层和感觉运动区。这项研究揭示了这种药物在调节患者这些区域的多动症方面的潜在效用。
Several psychiatric disorders involve abnormalities of interoception and associated neural circuitry centered on the insula. The development of interventions modulating interoceptive circuits could lead to novel treatment approaches for these disorders. The 5-HT3 receptor antagonist ondansetron is a good candidate for the modulation of interoceptive circuits, as 5-HT3 receptors are located abundantly on sensory pathways and ondansetron has shown some clinical utility in disorders characterized by sensory and interoceptive abnormalities. The present study tested the ability of three different doses of ondansetron to engage neural regions involved in interoception to determine the drug’s utility as a therapeutic agent to target circuit abnormalities in patients. Fifty-three healthy subjects were randomized to receive a single 8-mg (n= 18), 16-mg (n= 17), or 24-mg (n= 18) dose of ondansetron and placebo before MRI scanning on separate days. Subjects performed an fMRI task previously shown to engage interoceptive circuitry in which they viewed videos depicting body movements/sensation and control videos. The results revealed a highly significant relationship between dosage and activation in bilateral insula, somatosensory and premotor regions, cingulate cortex, and temporal cortex for control but not body-focused videos. These effects were driven by a robust reduction in activation for ondansetron compared to placebo for the 24-mg group, with weaker effects for the 16-mg and 8-mg groups. In conclusion, high-dose ondansetron reduces activation of several areas important for interoception, including insula and sensorimotor cortical regions. This study reveals the potential utility of this drug in modulating hyperactivity in these regions in patients.