DRUG RESPONSES AND AROUSAL

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 有证据表明，黄体酮及其代谢物别孕酮可能具有快速的中枢神经系统活动，可能在应激反应的调节中发挥作用。在动物和人类中，血浆孕酮和别孕酮水平都会因应激刺激而增加，并可能对下丘脑-垂体-肾上腺轴功能产生负面调节作用。此外，别孕酮可以作为GABAA受体的内源性配体，在应激等生理条件下产生抗焦虑和镇静作用。 在本研究中，我们将探讨孕酮的应激抑制作用。我们将在健康的男性志愿者接受社会压力程序之前给他们注射黄体酮(25，50毫克)或安慰剂。我们将评估治疗对急性应激后果的影响，包括主观状态(例如，焦虑或刺激增加)、生理体征(心率和血压)和血浆激素水平(皮质醇、ACTH)的变化。如果在人类中得到证实，给予黄体酮的压力抑制作用及其神经活性代谢物别孕酮的抗焦虑效果可能会为广泛性焦虑症、恐慌症、抑郁症和药物滥用等神经精神疾病带来新的治疗策略。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There is evidence that progesterone and its metabolite, allopregnanolone, may have rapid CNS actions that could play a role in the modulation of stress responses. Plasma levels of progesterone and allopregnanolone are increased in response to stressful stimuli in both animals and humans and may negatively modulate hypothalamic-pituitary-adrenal axis function. Additionally, allopregnanolone may act as an endogenous ligand of the GABAA receptor producing anxiolytic-sedative effects under physiological conditions such as stress. In the present study, we will investigate the stress dampening effects of progesterone. We will administer progesterone (25, 50 mg) or placebo to healthy male volunteers before they undergo a social stress procedure. We will assess the effects of treatments upon the consequences of acute stress, including changes in subjective state (e.g., increased anxiety or stimulation), physiological signs (heart rate and blood pressure), and plasma hormone levels (cortisol, ACTH). If confirmed in humans, the stress-dampening effect of progesterone administration and the anxiolytic efficacy of its neuroactive metabolite allopregnanolone may lead to new treatment strategies for neuropsychiatric disorders such as generalized anxiety disorder, panic disorder, depression, and drug abuse.