GENDER AND ESTROUS CYCLE EFFECTS ON 5-HT1A RECEPTORS

描述(改编自申请人的摘要)：建议的研究将 检验躯体树突状细胞5-HT1a受体功能的假设 在雌性发情周期中的调节，在雄性和雌性中是不同的 大鼠，并受雌激素调节。5-羟色胺1a(5-HT1a) 5-羟色胺神经元的自身受体已被认为是可能的 中枢神经系统5-羟色胺能神经元的性别差异 功能。人类女性是抗抑郁剂和 抗焦虑药物，但大多数动物模型研究都是进行的 在男性身上。最近的证据表明，人类女性 对各种情绪障碍的易感性可能存在于性别和/或 神经递质系统的生殖周期特异性调节 这是这些情绪失调的根本原因。拟议中的实验旨在 解决了发情前期雌性大鼠和 雌激素治疗的去卵巢大鼠对 躯体树突状细胞5-HT1A自身受体激活。男性将被包括在 这些研究旨在评估这一假设中的性别差异 受体的功能。这些实验包括：(A)测量 微透析法测定男性和女性体内5-羟色胺的释放 雌性大鼠和去卵巢大鼠，用苯甲酸雌二醇治疗，以及 (B)评价5-HT1A型躯体树突状细胞受体的作用 激动剂8-羟基-2-(二正丙氨基)四氢呋喃(8-OH-DPAT)对5-羟色胺的作用 放手。躯体树突状细胞的5-HT1A受体被认为是一种常见的 几种抗抑郁和抗焦虑药物的作用部位。 因此，对性别、发情周期和荷尔蒙的理解 这一受体的调节可能对最终的身份识别有重要意义 导致人类女性易受感染的机制有哪些 情绪失调症。

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.