RESTORING NORMAL FREQUENCY AND DURATION OF FEMALE SEXUAL BEHAVIOR

恢复女性性行为的正常频率和持续时间

• 批准号: 8358197
• 负责人: DAVID H ABBOTT
• 金额: $ 4.61万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8358197
• 关键词: 8-Hydroxy-2-(di-n-propylamino)tetralin; Affect; Aggressive behavior; Agonist; Animals; Area; Attention; Behavioral; Biological Assay; Biological Models; Callithrix; Callithrix jacchus jacchus; Chronic; Clinical; Disease; Estradiol; Estrogens; Female; Frequencies; Funding; Genital system; Grant; HTR2A gene; Hormonal; Hormones; Human; Intervention; Mammals; Menopause; National Center for Research Resources; Neurons; Pharmacotherapy; Prefrontal Cortex; Primates; Principal Investigator; Progestins; Publications; Research; Research Infrastructure; Resources; Safety; Serotonin; Serotonin Receptor 5-HT1A; Services; Sex Behavior; Sexual Dysfunction; Source; System; United States National Institutes of Health; Wisconsin; Woman; cost; flibanserin; improved; male; neuromechanism; nonhuman primate; postsynaptic; receptor; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Objective: To improve our understanding of serotonin-related neural mechanisms regulating female sexual response in marmosets in order to develop more appropriate clinical intervention for sexual hypofunction in women. Sexual dysfunction affects an estimated 43% of women. Currently there are no approved drug therapies for this disorder. Safety concerns about hormonal treatment with estrogens and progestogens motivates the search for non-steroidal pharmoacotherapy. The serotonin (5-HT) neuronal system has been implicated in regulating sexual behavior in a range of female mammals, including humans and nonhuman primates, but the mechanisms involved are not well understood. We developed a model system with female common marmosets to demonstrate that flibanserin stimulation of 5-HT1A (agonist) and 5-HT2A (antagonist) postsynaptic receptors increases male attention to female genital area without altering female sexual behavior, while chronic stimulation of pre- and post-synpatic 5-HT1A receptors by 8-OH-DPAT diminishes female sexual receptivity. Flibanserin also encourages a positive dynamic (allogrooming) between treated females and their male pairmates, in contrast to the negative dynamic engaged by 8-OH-DPAT (aggression, sexual rejection of the male). Postsynaptic action of flibanserin may be preferentially focused on the prefrontal cortex. As there were no observed behavioral differences between females receiving estradiol or no hormone, flibanserin may counteract low sexual desire in women, before or after menopause, by supporting positive interactions with their partner. This research used WNPRC Assay Services and Animal Services. Publications are pending.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的首席研究员可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 目的：提高对狨猴血清素相关调节雌性性反应的神经机制的认识，以便为女性性功能减退制定更合适的临床干预措施。 据估计 43% 的女性患有性功能障碍。目前还没有批准的药物治疗这种疾病。对雌激素和孕激素激素治疗的安全性担忧促使人们寻找非甾体药物疗法。血清素 (5-HT) 神经元系统与调节一系列雌性哺乳动物（包括人类和非人类灵长类动物）的性行为有关，但所涉及的机制尚不清楚。我们开发了一个雌性普通狨猴模型系统，以证明氟班色林刺激 5-HT1A（激动剂）和 5-HT2A（拮抗剂）突触后受体可增加雄性对雌性生殖器区域的注意力，而不会改变雌性性行为，而长期刺激前和8-OH-DPAT 的突触后 5-HT1A 受体会降低女性性接受能力。氟班色林还鼓励接受治疗的雌性与其雄性伴侣之间的积极动态（互容），这与 8-OH-DPAT 所产生的负面动态（攻击性、对雄性的性排斥）形成鲜明对比。氟班色林的突触后作用可能优先集中在前额皮质。由于接受雌二醇或不接受激素的女性之间没有观察到行为差异，因此氟班色林可以通过支持与伴侣的积极互动来抵消绝经前后女性性欲低下的影响。 本研究使用了 WNPRC 检测服务和动物服务。 出版物待定。