Neurobiology of Female Sexual Desire
女性性欲的神经生物学
基本信息
- 批准号:10260871
- 负责人:
- 金额:$ 5.61万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-03-15 至 2024-02-29
- 项目状态:已结题
- 来源:
- 关键词:ArousalBehavioralClinicalDendritic SpinesDevelopmentDiseaseDopamineDrug ApprovalElementsEyeFemaleGlutamatesGoalsHamstersIndividualMediatingMesocricetus auratusModelingMorphologyNeurobiologyNucleus AccumbensPathway interactionsPharmaceutical PreparationsPharmacologyPre-Clinical ModelProceduresPropertyReportingResearchRewardsSex BehaviorSexual ArousalSexual DysfunctionSignal PathwaySpousesTestingTherapeuticTranslatingWomanbasedesigndesigner receptors exclusively activated by designer drugseffective therapyexperienceinterestmalemesolimbic systemmolecular targeted therapiespressurepublic health relevancerelating to nervous systemsexual debuttherapeutic developmenttherapeutic targetwillingness
项目摘要
DESCRIPTION
Sexual dysfunction in women is primarily characterized by low levels of sexual arousal and
desire. Because no effective treatments exist for disorders of sexual desire in women, the FDA
was pressured to fast-track approval for the drug Addyi despite the absence of clinical evidence
that the drug provided any therapeutic benefit. Underlying the inability to construct a rational
approach to developing therapeutics for disorders of sexual desire in women is the lack of
research on the mechanistic basis for female sexual desire in pre-clinical models. We have
developed a Syrian hamster model of sexual desire that captures several essential elements
needed to translate the findings to women. We developed a procedure to evaluate the
rewarding properties of female sexual behavior, an element reported to be lacking in women
with low sexual desire. Women with low sexual desire also do not initiate sexual contacts with
their spouse or partner. In this regard we discovered an experimental approach to test the
female hamster's willingness to initiate sexual contacts with a male. Based on these hamster
studies we demonstrated that the rewarding consequences of sexual interactions with a male
feed forward to increase the female's sexual contacts. We further identified the mesolimbic
dopamine system, and prefrontal glutamatergic afferents, centered on the nucleus accumbens,
as a critical neural node mediating the rewarding effects of sexual behavior in females. The
research in this proposal takes three specific approaches to establish a programmatic
understanding of the neurobiology of female sexual desire. In the first aim we will use inhibitory
DREADDs to determine the relative contribution of dopamine and glutamate afferents to the
nucleus accumbens to the development of sexual reward and initiation of sexual interactions
with the male in our hamster model. We will also examine the contributions of these afferents to
changes in dendritic spine morphology consequent to female sexual experience. The second
aim takes a discovery approach to examining three possible intracellular signaling pathways
mediating the effects of sexual experience on behavioral and morphological plasticity. The last
aim will pharmacologically manipulate the individual signaling pathways to identify which of
these pathways are potential molecular targets for therapeutic development to treat problems of
sexual desire in women. Collectively this research will take a systematic approach to developing
a neurobiology of female sexual desire with an eye to the rational development of effective
therapies.
描述
女性性功能障碍的主要特征是低度性唤起和
欲望。由于目前还没有有效的治疗女性性欲障碍的方法,FDA
尽管缺乏临床证据,但仍被迫快速批准药物Addyi
这种药物有任何治疗效果。其根本原因是无法构建理性的
发展治疗女性性欲障碍的方法是缺乏
临床前模型中女性性欲的机制基础研究。我们有
开发了一种叙利亚仓鼠的性欲模型,它捕捉到了几个基本元素
需要将这些发现翻译给女性。我们开发了一个程序来评估
女性性行为的奖赏特性,据报道这是女性所缺乏的元素
性欲低下。性欲低下的女性也不会主动与
他们的配偶或伴侣。在这方面,我们发现了一种实验方法来测试
雌性仓鼠愿意与雄性仓鼠进行性接触。基于这些仓鼠
我们的研究表明,与男性发生性关系的有益后果
前馈以增加女性的性接触。我们进一步确定了中边缘
多巴胺系统和前额叶谷氨酸能传入,集中在伏核,
作为一个关键的神经节点,在女性性行为的奖赏效应中起着中介作用。这个
本提案中的研究采用三种具体方法来建立一个方案
了解女性性欲的神经生物学。在第一个目标中,我们将使用抑制
DREADDS以确定多巴胺和谷氨酸传入对
伏隔核对性奖赏的发育和性互动的起始性作用
和我们仓鼠模型里的雄性。我们还将研究这些传入细胞对
女性性行为后树突棘形态的变化。第二
Aim采用发现的方法来研究三种可能的细胞内信号通路
介导性体验对行为和形态可塑性的影响。最后
AIM将在药理学上操纵单个信号通路,以识别哪些
这些通路是潜在的分子靶点,可用于治疗骨肉瘤。
女性的性欲。总的来说,这项研究将采取系统的方法来开发
神经生物学对女性性欲的着眼于理性发展的有效
治疗。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Robert L Meisel其他文献
Robert L Meisel的其他文献
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{{ truncateString('Robert L Meisel', 18)}}的其他基金
A Longitudinal Mentoring Approach to Increase Diversity Among Researchers of Neurological Disorders
增加神经系统疾病研究人员多样性的纵向指导方法
- 批准号:
10221787 - 财政年份:2020
- 资助金额:
$ 5.61万 - 项目类别:
A Longitudinal Mentoring Approach to Increase Diversity Among Researchers of Neurological Disorders
增加神经系统疾病研究人员多样性的纵向指导方法
- 批准号:
10023446 - 财政年份:2020
- 资助金额:
$ 5.61万 - 项目类别:
A Longitudinal Mentoring Approach to Increase Diversity Among Researchers of Neurological Disorders
增加神经系统疾病研究人员多样性的纵向指导方法
- 批准号:
10469981 - 财政年份:2020
- 资助金额:
$ 5.61万 - 项目类别:
A Longitudinal Mentoring Approach to Increase Diversity Among Researchers of Neurological Disorders
增加神经系统疾病研究人员多样性的纵向指导方法
- 批准号:
10678678 - 财政年份:2020
- 资助金额:
$ 5.61万 - 项目类别:
Organization for the Study of Sex Differences Annual Meeting
性别差异研究组织年会
- 批准号:
9045419 - 财政年份:2014
- 资助金额:
$ 5.61万 - 项目类别:
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