Neuroanatomy and neurochemistry of sexual behavior

性行为的神经解剖学和神经化学

• 批准号: RGPIN-2018-05439
• 负责人: Pfaus, James
• 金额: $ 4.01万
• 依托单位: Concordia University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=662059
• 关键词: Neuroanatomy; neurochemistry; sexual; behavior

The main objective of the proposed research is to continue our identification of specific neuroanatomical and neurochemical systems that excite or inhibit appetitive and consummatory aspects of sexual behavior in male and female rats. We have concentrated our efforts in the previous grant cycle around understanding the excitatory role of the medial preoptic area (mPOA) of the anterior hypothalamus and its interaction with regions of the ventromedial hypothalamus, ventral tegmental area (VTA), and medial amygdala. The proposed research will extend this work to investigate the role played by dopamine, oxytocin, vasopression, melanocortins, and opioids, in controlling appetitive sexual behaviors, and how those neurochemical systems are activated by unconditioned and conditioned olfactory, somatosensory, and genital stimuli. Recently, we have turned our attention to the role of cortical structures in sexual inhibition, notably the medial prefrontal, cingulate, and insular cortices, and their outputs to the mPOA, VTA, and nucleus accumbens (NAc). We propose to examine the role played by serotonin in these regions in the "top-down" control of sexual inhibition using paradigms established in our lab of sexual refractoriness in male rats, estrus termination in female rats, conditioned inhibition, and alcohol-induced disinhibition. We are also interested in the role played by first experiences with sexual reward and how they alter, via epigenetic mechanisms, the activation of excitatory systems. The proposed research will utilize a combination of neuropharmacological techniques, including in vivo neurochemical analyses using receptor-selective antagonists, autoradiography, molecular biological techniques for staining activated neurons in tissue, and epigenetic techniques to inactivate demethylation enzymes, to examine the role of different brain regions and neurochemical systems. A second related line of research seeks to understand the role played by clitoral stimulation (CLS) in female rat sexual reward and appetitive sexual motivation. We have found that CLS induces conditioned place preference, and activates regions of the mPOA, VTA, NAc, and amygdala. We have also recently discovered that such stimulation also induces an orgasm-like response in females, accompanied by specific vocalization patterns that resemble those in male rats during penile stimulation and after ejaculation (although the female pattern is higher in the kHz range and more complex). We propose to examine how these responses depend on steroid hormone priming, and are altered by sexual nonreward induced by opioid antantagonism, conditioned association with sexually nonreceptive partners, or by SSRIs that inhibit orgasm. These studies will take our research to the next level by examining the activation of neurochemical and molecular systems associated with sexual excitation and inhibition.

这项拟议研究的主要目标是继续我们的特定神经解剖学和神经化学系统的鉴定，这些系统刺激或抑制雄性和雌性大鼠性行为的食欲和性欲方面。我们在前一个资助周期中集中精力了解下丘脑前内侧视前区(MPOA)的兴奋作用及其与下丘脑腹内侧区、腹侧被盖区(VTA)和杏仁内侧核的相互作用。这项拟议的研究将扩展这项工作，以调查多巴胺、催产素、血管加压素、黑素皮质素和阿片类药物在控制食欲性行为中所起的作用，以及这些神经化学系统是如何被无条件和条件性嗅觉、躯体感觉和生殖器刺激激活的。最近，我们将注意力转向皮质结构在性抑制中的作用，特别是内侧前额叶、扣带和岛叶皮质，以及它们向mPOA、VTA和伏隔核(NAC)的输出。我们建议使用我们实验室建立的雄性大鼠性顽固性、雌性大鼠发情终止、条件抑制和酒精诱导去抑制的范例，来研究这些区域中5-羟色胺在“自上而下”控制性抑制中所起的作用。我们还感兴趣的是，性奖励的第一次体验所起的作用，以及它们如何通过表观遗传机制改变兴奋系统的激活。这项拟议的研究将结合神经药理学技术，包括使用受体选择性拮抗剂的体内神经化学分析，放射自显影，组织中激活神经元染色的分子生物学技术，以及灭活去甲基化酶的表观遗传学技术，以检查不同大脑区域和神经化学系统的作用。第二个相关的研究试图了解阴蒂刺激(CLS)在雌性大鼠性奖赏和欲望性动机中所起的作用。我们发现，CLS诱导条件性位置偏爱，并激活mPOA、VTA、NAC和杏仁核区域。我们最近还发现，这种刺激也会在雌性大鼠身上诱导性高潮样的反应，伴随着特定的发声模式，类似于雄性大鼠在阴茎刺激和射精后的发声模式(尽管雌性大鼠的发声模式在khz范围内更高，也更复杂)。我们建议研究这些反应如何依赖于类固醇激素的启动，以及如何被阿片类药物拮抗诱导的性无奖赏、与不接受性行为的伴侣的条件性联系或抑制性高潮的SSRI改变。这些研究将通过检测与性兴奋和性抑制相关的神经化学和分子系统的激活，将我们的研究带到一个新的水平。