Sex Differences in Progesterone Effects on Responses to stress and drug cues

黄体酮的性别差异对压力和药物提示反应的影响

基本信息

  • 批准号:
    7661657
  • 负责人:
  • 金额:
    $ 21.99万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
  • 资助国家:
    美国
  • 起止时间:
  • 项目状态:
    未结题

项目摘要

Stress, drug cue exposure and cocaine itself potently stimulate stress and reward systems in the brain and each increase drug craving, thereby increasing the susceptibility to relapse. Women, in particular, show a greater stress and negative affect related susceptibility to relapse. Previous SCOR-related research shows clear sex differences in stress responses, behavioral effects of cocaine and in negative affect and anxiety associated with cocaine craving and stress related relapse susceptibility. However, no previous research has examined the basis of sex differences in stress and cue induced craving and arousal, both of which are known to increase relapse susceptibility. Cumulating evidence suggest that gonadal hormones, estradiol (E) and progesterone (P), may contribute to these sex differences. While E enhances behavioral responses to cocaine, P attenuates subjective, behavioral and physiological responses to cocaine. Whether gonadal hormones such as progesterone affect stress and drug cue-induced craving, and mediate vulnerability to cocaine relapse, especially in women has been studied thus far. Our preliminary findings in cocaine dependent women suggested that high levels of luteal phase P was associated with decreases in stress and drug cue-induced drug seeking, anxiety and blood pressure responses. On the basis of these data, we hypothesize that progesterone treatment vs. placebo will decrease stress and drug cue-induced cocaine craving, negative affect and alter physiological and HPA responses to stress, and these changes will be greater in women than men. In a sample of 120 treatment-seeking cocaine dependent men and women (60 men and 60 women), the following specific aims are proposed: (1) to examine if progesterone alters stress and cue-induced craving, anxiety and negative emotion responses in cocaine dependent men and women, with sex differences in these effects; (2) To assess progesterone's sex-specific effects on HPA axis measures (ACTH, cortisol and prolactin) during stress and drug cue exposure; (3) To examine progesterone's sex-specific effects on cardiovascular responses to stress and drug cue exposure and to assess its effects on plasma catecholamines; (4) To explore whether progesterone's effects on craving, HPA axis and sympathetic responses are associated with neuroactive steroids and whether these are differentially affected in men and women. Findings from this study will (A) provide a greater understanding of the effects of progesterone, a key gonadal hormone, and it's role in stress regulation, stress-related cocaine seeking and relapse vulnerability, and (B)contribute crucial information needed to develop progesterone as a potential pharmacotherapy to prevent stress-related cocaine relapse in women.
压力、药物暴露和可卡因本身都会强烈刺激大脑中的压力和奖励系统, 每一种都会增加对药物的渴望,从而增加复发的可能性。尤其是女性, 更大的压力和负面影响与复发的易感性有关。此前的SCOR相关研究显示, 在压力反应、可卡因的行为影响以及负面影响和焦虑方面存在明显的性别差异 与可卡因渴望和压力相关的复发易感性有关。然而,以前的研究没有 研究了压力和线索诱导的渴望和唤醒的性别差异的基础,这两个都是已知的 增加复发的可能性累积的证据表明,性腺激素,雌二醇(E)和 孕酮(P)可能是导致这些性别差异的原因。虽然E增强了行为反应, 可卡因,P减弱对可卡因的主观、行为和生理反应。是否性腺 激素如孕酮影响压力和药物线索诱导的渴望,并介导对 可卡因复吸,特别是妇女的复吸,迄今已进行了研究。我们对可卡因的初步发现 依赖性妇女认为,高水平的黄体期P与压力的减少有关, 药物线索诱导的药物寻求、焦虑和血压反应。根据这些数据,我们 假设孕酮治疗与安慰剂相比会减少压力和药物线索诱导的可卡因 渴望,负面影响和改变生理和HPA对压力的反应,这些变化将是 女性比男性更强。在120名寻求治疗的可卡因依赖男性和女性(60 男性和60名女性),提出了以下具体目标:(1)检查孕酮是否改变压力 以及可卡因依赖男性和女性的线索诱导的渴望,焦虑和负面情绪反应, (2)探讨孕酮对HPA轴的性别特异性作用 测量(ACTH,皮质醇和催乳素)在压力和药物线索暴露;(3)检查 孕激素对心血管反应的性别特异性影响 (4)探讨孕酮对大鼠的渴求、HPA的影响 轴和交感神经反应与神经活性类固醇有关, 影响男性和女性。这项研究的结果将(A)提供对影响的更好理解 孕酮,一种关键的性腺激素,它在压力调节中的作用, 和复发的脆弱性,和(B)提供关键信息,需要发展孕酮作为一个 潜在的药物治疗,以防止与压力有关的可卡因复吸的妇女。

项目成果

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Rajita Sinha其他文献

Rajita Sinha的其他文献

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{{ truncateString('Rajita Sinha', 18)}}的其他基金

Guanfacine Target Engagement and Validation to Improve Substance Use Outcomes in Women
胍法辛目标参与和验证以改善女性药物使用结果
  • 批准号:
    9899239
  • 财政年份:
    2019
  • 资助金额:
    $ 21.99万
  • 项目类别:
Neuroactive Steroid Potentiation to Decrease Alcohol Craving, Normalize HPA axis function and Prevent Alcohol Relapse
神经活性类固醇增强剂可减少酒精渴望、使 HPA 轴功能正常化并防止酒精复吸
  • 批准号:
    10201415
  • 财政年份:
    2018
  • 资助金额:
    $ 21.99万
  • 项目类别:
Neural and Neuroendocrine response to compulsive alcohol motivation
对强迫性酒精动机的神经和神经内分泌反应
  • 批准号:
    9316393
  • 财政年份:
    2016
  • 资助金额:
    $ 21.99万
  • 项目类别:
Food Cues, Stress, Motivation for Highly Palatable Foods and Weight Gain
食物暗示、压力、对美味食物的动机和体重增加
  • 批准号:
    8694030
  • 财政年份:
    2013
  • 资助金额:
    $ 21.99万
  • 项目类别:
Preventing childhood obesity through a family-based mindfulness intervention
通过基于家庭的正念干预预防儿童肥胖
  • 批准号:
    8512273
  • 财政年份:
    2013
  • 资助金额:
    $ 21.99万
  • 项目类别:
Preventing childhood obesity through a family-based mindfulness intervention
通过基于家庭的正念干预预防儿童肥胖
  • 批准号:
    8657012
  • 财政年份:
    2013
  • 资助金额:
    $ 21.99万
  • 项目类别:
Food Cues, Stress, Motivation for Highly Palatable Foods and Weight Gain
食物暗示、压力、对美味食物的动机和体重增加
  • 批准号:
    8598990
  • 财政年份:
    2013
  • 资助金额:
    $ 21.99万
  • 项目类别:
Food Cues, Stress, Motivation for Highly Palatable Foods and Weight Gain
食物暗示、压力、对美味食物的动机和体重增加
  • 批准号:
    9113208
  • 财政年份:
    2013
  • 资助金额:
    $ 21.99万
  • 项目类别:
Food Cues, Stress, Motivation for Highly Palatable Foods and Weight Gain
食物暗示、压力、对美味食物的动机和体重增加
  • 批准号:
    9069833
  • 财政年份:
    2013
  • 资助金额:
    $ 21.99万
  • 项目类别:
Chronic Alcohol and Brain Stress Circuit Response
慢性酒精和脑应激回路反应
  • 批准号:
    8019105
  • 财政年份:
    2009
  • 资助金额:
    $ 21.99万
  • 项目类别:

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