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Neuropharmacological studies on sex difference in the central effects of serotonin1A agonists

5-羟色胺1A激动剂中枢作用性别差异的神经药理学研究

基本信息

批准号：
04671413
负责人：
MATSUDA Toshio
金额：
$ 1.34万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

项目摘要

Neuropharmacological studies on the sex differences in the effects of sserotonin _<1A> (5-HT _<1A>) receptor agonists were carried out, in order to clarify the roles of sex hormone in functional relationship between serotonergic system and CRF.1. CRF stimulated the activity of adenylate cylase in membrane fraction of rat and mouse cerebral cortex and in homogenate of rat pituitary. There is sex difference in the stimulation. Chronic administration of 8-OH-DPAT, a typical 5-HT _<1A> agonist, did not affect CRF-stimulated adenylate cyclase activity in rat pituitary.2. CRF stimulated tyrosine hydorxylase activity a little in rat brain synaptosomes.3. Chronic administration of 8-OH-DPAT attenuated the increasing effect of serum corticosterone and the hypothermic effect in mice. The tolerance was observed in female mice faster than in male.4.Forced swimming stress, which releases CRF, stimulated norepinephrine metabolism, but not 5-HT metabolsim, in hypothalamus of rats.5.5-HT _<1A> receptor agonists did not affect interacellular Ca ^<2+> level, cAMP level and phosphoinositide metabolism in cultured rat astrocytes,These findings suggest that the sex difference in the effect of 5-HT _<1A> receptor agonists on hypotalumus-pituitary-adrenal axis is due to that in CRF release. Futher, the sex differences in the postsynaptic effects of 5-HT _<1A> receptor agonists does not appear to be due to those in the receptor and signal transduction systems.

为了阐明性激素在5-羟色胺能系统与CRF1功能关系中的作用，对5-羟色胺受体激动剂作用的性别差异进行了神经药理学研究。CRF对大鼠和小鼠大脑皮层膜组分和大鼠脑垂体匀浆中腺苷酸环酶活性均有刺激作用。在刺激上存在性别差异。长期给予8-OH-DPAT，一种典型的5-羟色胺激动剂，不影响CRF刺激的大鼠脑垂体腺苷环化酶的活性。CRF对大鼠脑突触体内酪氨酸羟基酶活性有一定的刺激作用。长期给予8-OH-DPAT可减弱小鼠血清皮质酮的升高效应和降温效应。4.游泳应激可刺激大鼠下丘脑去甲肾上腺素代谢，但不刺激5-羟色胺代谢。5.5-羟色胺受体激动剂对培养的大鼠星形胶质细胞细胞内钙、cAMP及磷脂酰肌醇代谢无明显影响，提示5-羟色胺受体激动剂对下丘脑-垂体-肾上腺轴的作用可能与CRF释放有关。此外，5-羟色胺受体激动剂突触后效应的性别差异似乎不是由于受体和信号转导系统的差异。