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

通过对5-羟色胺_<1A>（5-羟色胺_<1A>）受体激动剂作用的性别差异进行神经药理学研究，以阐明性激素在5-羟色胺能系统与CRF.1功能关系中的作用。CRF刺激了大鼠和小鼠大脑皮层膜组分和大鼠垂体匀浆中腺苷酸环化酶的活性。在刺激方面存在性别差异。慢性给药8-OH-DPAT（一种典型的5-HT <1A>激动剂）对crf刺激的大鼠垂体腺苷酸环化酶活性没有影响。CRF对大鼠脑突触体酪氨酸羟化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作用和降体温作用。雌性小鼠的耐受性明显快于雄性小鼠。强迫游泳应激释放CRF，刺激大鼠下丘脑去甲肾上腺素代谢，但不影响5-HT代谢。5.5- ht <1A>受体激动剂不影响培养大鼠星形胶质细胞胞间Ca ^<2+>水平、cAMP水平和磷酸肌肽代谢，提示5-HT <1A>受体激动剂对下丘脑-垂体-肾上腺轴影响的性别差异是由于CRF释放的差异。此外，5-HT <1A>受体激动剂的突触后作用的性别差异似乎不是由于受体和信号转导系统的差异。

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.