Progestins non-genomic actions for socio-sexual behavior

孕激素对社会性行为的非基因组作用

• 批准号: 7252507
• 负责人: CHERYL Anne FRYE
• 金额: $ 22.16万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT ALBANY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7252507
• 关键词: Adrenal Glands; Affective; Affinity; Aggressive behavior; Agonist; Anabolism; Animal Model; Anxiety; Attenuated; Behavior; Behavioral; Benzodiazepine Receptor; Binding; Brain; Complex; Corticosterone; D Aspartate; Data; Diestrus; Disease; Emotions; Endocrine Glands; Endocrinology; Enzymes; Excitatory Amino Acid Antagonists; Exploratory Behavior; Female; Functional disorder; GABA-A Receptor; Genomics; Glutamate Receptor; Hydroxysteroids; Hypothalamic structure; Incidence; Individual; Infusion procedures; Knowledge; Lordosis; Mediating; Metabolism; Methods; Midbrain structure; Modeling; N-Methylaspartate; Nature; Neurobiology; Neuroglia; Nociception; Ovarian; Oxidoreductase; Partner in relationship; Peripheral; Pharmacology; Posture; Proestrus; Progesterone; Progesterone Receptors; Progestins; Radioimmunoassay; Rattus; Relative (related person); Reproduction; Research; Rodent; Role; Sex Behavior; Social Behavior; Source; Stimulus; Stress; System; Testing; Variant; Ventral Tegmental Area; neuropsychiatry; non-genomic; novel; pregnane-20-one; primin; receptor; research study; response; sex; social; social attachment

DESCRIPTION (provided by applicant): Progestins mediate the onset and duration of the mating posture, lordosis, in female rodents through actions in the hypothalamus and ventral tegmental area (VTA). In the hypothalamus, progesterone (P) has traditional, "genomic" actions via intracellular progestin receptors (PRs). In the VTA, 3a-hydroxy-5a-pregnan-20-one (3a,5a-THP) has "non-genomic" actions independent of PRs to facilitate lordosis that may involve GABA-Benzodiazepine receptors (GBRs) and/or NMDA type glutamate receptors (NMDARs). In addition to lordosis, 3a,5a-THP may influence other social behaviors, as well as exploration and anxiety. Levels of 3a,5a-THP can also change with behavioral and/or environmental stimuli. Thus, experiments will test the hypothesis that rapid biosynthesis of, or metabolism to, 3a,5a-THP and its non-genomic actions at GBRs and/or NMDARs influence social and sexual behaviors (socio-sexual behaviors) and socio-sexual behaviors alter central 3a,5a-THP concentrations via similar mechanisms. Using classic behavioral endocrinology, pharmacology, and radioimmunoassay methods in a model of socio-sexual behaviors, experiments will investigate: 1) the causal effects of 3a,5a-THP in the midbrain VTA to facilitate socio-sexual behaviors. 2) The effects of various socio-sexual behaviors on midbrain 3a,5a-THP levels. If midbrain 3a,5a-THP is altered in response to socio-sexual behaviors, then this will suggest 3a,5a-THP in the midbrain mediates, and can be reflexively altered by, socio-sexual stimuli. 3) 3a,5a-THP can be formed in the VTA from metabolism of progestins produced peripherally by endocrine glands or centrally via biosynthesis in glial cells. The relative importance of 3a,5a-THP in the VTA from central biosynthesis vs metabolism of peripheral progestins to effect, or be increased by, socio-sexual behaviors will be investigated. 4) 3a,5a-THP may have actions at non-genomic substrates, such as GBRs and/or NMDARs. Whether behavioral effects of 3a,5a-THP, or 3a,5a-THP formation in response to socio-sexual behaviors, are in part due to non-genomic actions at these receptors in the VTA will be examined. Together, these experiments will elucidate the function, source, and mechanisms of 3a,5a-THP's actions in the VTA for socio-sexual behaviors and reveal how 3a,5a-THP increases in response to these behaviors. This research, investigating novel behavioral functions of 3a,5a-THP, will extend knowledge of the neurobiology of progestins, relevant for socio-sexual behaviors, and their connections to systems that regulate emotions. 3a,5a-THP is implicated in stress and the pathophysiology and treatment of neuropsychiatric disorders. Thus, 3a,5a-THP's role and actions to enhance reproduction and social bonds, minimize aggression, influence affective aspects of social behaviors, and to mediate responses to behavioral and/or environmental stimuli needs to be understood.

描述（由申请人提供）：孕激素通过下丘脑和腹侧被盖区（VTA）的作用介导雌性啮齿动物交配姿势前倾的发生和持续时间。在下丘脑中，黄体酮(P)通过细胞内黄体酮受体（pr）具有传统的“基因组”作用。在VTA中，3a-hydroxy-5a-pregnan-20-one （3a,5a-THP）具有独立于pr的“非基因组”作用，促进前凸，可能涉及gaba -苯二氮卓类受体（GBRs）和/或NMDA型谷氨酸受体（NMDARs）。除了前凸，3a，5a-THP还可能影响其他社会行为，以及探索和焦虑。3a，5a-THP水平也会随着行为和/或环境刺激而改变。因此，实验将验证这样的假设，即3a，5a-THP的快速生物合成或代谢及其在gbr和/或NMDARs上的非基因组作用影响社会和性行为（社会-性行为），而社会-性行为通过类似的机制改变中心3a，5a-THP浓度。利用经典的行为内分泌学、药理学和放射免疫分析方法，在社会-性行为模型中，实验将探讨：1)中脑VTA中3a，5a-THP促进社会-性行为的因果关系。2)不同社会性行为对中脑3a，5a-THP水平的影响。如果中脑3a，5a-THP在对社会性行为的反应中发生改变，那么这将表明中脑3a，5a-THP介导，并且可以被社会性刺激反射性地改变。3) 3a，5a-THP可在VTA内由外周内分泌腺体或中枢神经胶质细胞生物合成的孕激素代谢形成。在VTA中，3a，5a-THP从中枢生物合成到外周孕激素代谢的相对重要性将被研究，以影响或增加社会性行为。4) 3a，5a-THP可能作用于非基因组底物，如gbr和/或NMDARs。是否3a，5a-THP或3a，5a-THP形成对社会性行为的行为影响部分是由于VTA中这些受体的非基因组作用将被研究。总之，这些实验将阐明3a，5a-THP在VTA中对社会性行为的作用的功能，来源和机制，并揭示3a，5a-THP如何对这些行为做出反应。这项研究旨在研究3a，5a-THP的新行为功能，将扩展黄体酮的神经生物学知识，与社会性行为相关，以及它们与调节情绪的系统的联系。3a，5 - thp与应激、神经精神疾病的病理生理和治疗有关。因此，需要了解3a，5a-THP在增强繁殖和社会联系，减少攻击，影响社会行为的情感方面以及调节对行为和/或环境刺激的反应方面的作用和作用。