Corley K C, Singh V B, Phan T H, Boadle-Biber M C
Department of Physiology, Virginia Commonwealth University, Richmond 23298.
Eur J Pharmacol. 1992 Mar 31;213(3):417-25. doi: 10.1016/0014-2999(92)90631-d.
Pretreatment (15 min) of male rats with gepirone given parenterally (10 mg/kg i.p.) or intracranially into the dorsal raphe nucleus (14 or 21 micrograms) 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-pyrimidinyl)-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.
对雄性大鼠进行预处理（15分钟），通过腹腔注射给予吉哌隆（10毫克/千克）或向中缝背核颅内注射（14或21微克），可阻断急性声音应激1小时后体外观察到的脑色氨酸羟化酶活性和5-羟吲哚胺乙酸组织水平的快速可逆性增加。连续28天进行慢性吉哌隆治疗（皮下注射40毫克/天）可预防由重复声音应激引起的稳定酶活性增加，以及声音应激后始终观察到的快速可逆性增加。在这些实验中，吉哌隆的代谢产物1-(2-嘧啶基)-1-哌嗪均无活性。每次声音呈现时都会出现短暂的血压升高，但重复声音应激暴露后未观察到持续性高血压。吉哌隆可能通过抑制中缝背核中血清素能神经元放电来阻断声音应激诱导的生化增加，而这种抑制是由其在胞体树突（5-HT1A）自身受体上的激动剂作用介导的。
