GENDER AND ESTROUS CYCLE EFFECTS ON 5-HT1A RECEPTORS

描述（改编自申请人摘要）：拟定研究将 测试体树突5-HT1A受体功能是 在雌性发情周期中调节，在雄性和雌性中不同 大鼠，并由雌激素调节。 5-羟色胺1A（5-HT1A） 5-羟色胺神经元的自身受体被认为是 促进中枢神经系统神经递质的性别差异 功能 人类女性是抗抑郁药的主要消费者， 抗焦虑药物，但大多数研究与动物模型已进行 在男性中。 最近的证据表明人类女性 易受各种情绪障碍的影响可能存在于性别和/或 生殖周期特异性调节神经递质系统， 这些情绪障碍的根源 拟议的实验旨在 解决了这一假设，即发情前期雌性大鼠和 雌激素处理卵巢切除大鼠对 体树突5-HT 1A自身受体激活。 男性将被纳入 这些研究，以评估假定的性别差异， 受体的功能。 包括在实验中的是：（a）测量 5-HT的释放，如通过微透析程序在男性和 雌性大鼠和卵巢切除大鼠，用苯甲酸雌二醇处理，和 (b)5-HT 1A体树突受体作用的评价 5-HT激动剂，8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT） release. 体树突5-HT1A受体被认为是一种常见的 几种抗抑郁和抗焦虑药物作用部位。 因此，对性别、发情周期和激素的理解 这种受体的调节可能对最终鉴定 人类女性脆弱性增强的机制 情绪障碍

DESCRIPTION (Adapted from applicant's abstract): The proposed studies will test the hypotheses that somatodendritic 5-HT1A receptor function is modulated during the female estrous cycle, is different in male and female rats, and is modulated by estrogen. The somatodentric serotonin 1A (5-HT1A) autoreceptor of serotonin neurons has been targeted as a possible contributor to gender differences in central nervous system serotonergic function. Human females are the major consumers of antidepressant and antianxiety drugs, but most research with animal models has been performed in males. Recent evidence suggests that the human female's enhanced vulnerability to various mood disorders could reside in gender- and/or reproductive cycle-specific modulation of neurotransmitter systems that underlie these mood dysfunctions. The proposed experiments are designed to address the hypothesis that the proestrus female rat and the estrogen-treated ovariectomized rat have a reduced sensitivity to somatodendritic 5-HT1A autoreceptor activation. Males will be included in these studies in order to evaluate the putative gender difference in this receptor's function. Included in the experiments are: (a) a measurement of the release of 5-HT as estimated by microdialysis procedures in male and female rats and in ovariectomized rats, treated with estradiol benzoate, and (b) evaluation of the effects of the 5-HT1A somatodendritic receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), on 5-HT release. The somatodendritic 5-HT1A receptor is believed to be a common site of action for several antidepressant and antianxiety drugs. Consequently, an understanding of the gender, estrous cycle, and hormonal modulation of this receptor could have significance to the eventual identity of the mechanisms responsible for the human female's enhanced vulnerability to mood disorders.