海马神经元型一氧化氮合酶神经元再生通路介导5-羟色胺类抗抑郁药作用

Hippocampal nNOS-neuronal regeneration pathways mediates the effect of 5-serotonin antidepressive drugs

目的:研究5-羟色胺类抗抑郁药的作用机制。方法:将经典5-羟色胺类抗抑郁药氟西汀及选择性5-HT1A受体激动剂8-OH-DPAT,通过立体定位特异性注射到野生型和神经元型一氧化氮合酶(nNOS)敲除型小鼠海马部位,通过Brdu免疫组化和新奇摄食抑制试验、强迫游泳试验、悬尾试验等抑郁行为学检测,观察神经元再生的变化情况和抗抑郁效果。结果:氟西汀和8-OH-DPAT通过nNOS上调海马神经元再生,发挥抗抑郁作用。结论:海马nNOS-神经元再生通路介导5-羟色胺类抗抑郁药的抗抑郁作用。

AIM. To explore the antidepres- sive mechanism of serotonin reuptake inhabitor and selective 5-HT1A receptor agonist. METH- ODS. Fluoxetine, a serotonin reuptake inhibi- tor, and 8-OH-DPAT, a selective 5-HT1A re- ceptor agonist, were infused into the dentate gy- rus （DG） of bilateral hippocampus of nNOS knockout and wild-type mice by stereotactic sur- gery. Brdu immunohistochemisty was performed to detect neurogenesis as well as novelty sup- pressed feeding test, forced swimming test and tail suspending test were used to measure de-pression-related behavior. RESULTS： Both selec- tive infusion of fluoxetine and 8-OH-DPAT into hippocampus up-regulated neurogenesis and gen- erated antidepressant- like effect, which were dependent on the function of nNOS. CONCLU- SION： nNOS-neurogenesis cascade in the hippo- campus mediates the antidepressive effect of se- rotonin reuptake inhabitor and selective 5-HT1A receptor agonist.