Knockout mice reveal opposite roles for serotonin 1A and 1B receptors in prepulse inhibition
Knockout mice reveal opposite roles for serotonin 1A and 1B receptors in prepulse inhibition
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DOI：
10.1016/s0893-133x(99)00164-5
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发表时间：
2000-06-01
影响因子：
7.6
通讯作者：
Geyer, MA
中科院分区：
文献类型：
--
作者：
Dulawa, SC;Gross, C;Geyer, MA
多巴胺能系统参与调节精神分裂症患者缺乏的前脉冲抑制（PPI）和惊吓习惯化。PPI是当一个微弱的“前脉冲”先于一个惊人的刺激30-500毫秒时发生的惊吓幅度的减少。使用野生型（WT）、5-HT（1A）敲除（1AKO）和5-HT（1B）敲除（1BKO）小鼠检测5-HT（1A）和5-HT（1B）受体在调节PPI和习惯化中的作用。5-HT（1A/1B）激动剂RU 24969降低WT和1AKO小鼠的PPI和习惯化，但不降低1BKO小鼠的PPI和习惯化，而5-HT（1A）激动剂8-OH-DPAT增加WT和1BKO小鼠的PPI，但不增加1AKO小鼠的PPI。类似地，选择性5-HT（1B）激动剂安吡托林降低了WT小鼠的PPI，但在1BKO小鼠中没有。在使用完整的129 Sv小鼠的实验中，5-HT（1A）激动剂flesinoxan增加了PPI，而安吡托林降低了PPI和习惯性。研究结果表明，5-HT（1B）受体激活降低PPI和习惯性，5-HT（1A）受体激活增加PPI。
The serotonergic system is involved in the modulation of prepulse inhibition (PPI) and habituation of startle, which are deficient in schizophrenia patients. PPI is the reduction in startle amplitude that occurs when a weak "prepulse" precedes a startling stimulus by 30-500 msec. The roles of 5-HT(1A) and 5-HT(1B) receptors in modulating PPI and habituation were examined using wild-type (WT), 5-HT(1A) knockout (1AKO), and 5-HT(1B) knockout (1BKO) mice. The 5-HT(1A/1B) agonist RU24969 reduced PPI and habituation in WT and 1AKO, but not 1BKO mice, whereas the 5-HT(1A) agonist 8-OH-DPAT increased PPI in WT and 1BKO, but not in 1AKO mice. Similarly, the selective 5-HT(1B) agonist anpirtoline reduced PPI in WT, but not in 1BKO mice. In experiments using intact 129Sv mice, the 5-HT(1A) agonist flesinoxan increased PPI while anpirtoline decreased PPI and habituation. Findings suggest that 5-HT(1B) receptor activation decreases PPI and habituation, and 5-HT(1A) receptor activation increases PPI in mice.