Effect of gepirone on increases in tryptophan hydroxylase in response to sound stress.
Effect of gepirone on increases in tryptophan hydroxylase in response to sound stress.
复制标题
DOI：
10.1016/0014-2999(92)90631-d
复制
发表时间：
1992-03
影响因子：
5
通讯作者：
K. Corley;Virendra B. Singh;T. Phan;M. Boadle-Biber
中科院分区：
文献类型：
--
作者：
K. Corley;Virendra B. Singh;T. Phan;M. Boadle-Biber
用胃肠外给予的吉吡隆（10 mg/kg i. p.）或脑内注入中缝背核（14或21 μg）可阻断急性声应激1小时后体外观察到的脑色氨酸羟化酶活性和5-羟基吲哚胺乙酸组织水平的快速可逆增加。吉哌隆长期治疗28天（40 mg/天s.c.）阻止了由重复的声应力引起的稳定的酶活性增加，以及在声应力之后总是观察到的快速可逆的增加。吉哌隆代谢产物1-（2-嘧啶基）-1-哌嗪在这些实验中均无活性。短暂的血压升高发生在每一个声音介绍，但没有观察到持续性高血压与重复的声音应激暴露。吉哌隆可能通过抑制中缝背核中的多巴胺能神经元放电来阻断声音应激诱导的生化增加，该抑制由其对体树突（5-HT 1A）自身受体的激动剂作用介导。
Pretreatment (15 min) of male rats with gepirone given parenterlly (10 mg/kg i.p.) or intracranially into the dorsal raphe nucleus (14 or 21 μg) blocks the rapidly reversible increase in brain tryptophan hydroxylase activity and 5-hydroxyindolamine acetic acid tissue levels seen in vitro after 1-h acute sound stress. Chronic gepirone treatment over 28 days (40 mg/day s.c.) prevents the stable enzyme activity increase induced by repeated sessions of sound stress, and the rapidly reversible increase always observed following sound stress. The gepirone metabolite, 1-(2-pyrmidinyl)-1-piperazine, is inactive in each of these experiments. Transient blood pressure elevations occur with each sound presentation, but no persistent hypertension is observed with repeated sound-stress exposures. Gepirone may block the sound stress-induced biochemical increases by its inhibition of serotonergic neuronal firing in the dorsal raphe nucleus that is mediated by its agonist action at the somatodendritic (5-HT1A) autoreceptors.