Gender Differences in Drug Abuse

药物滥用的性别差异

• 批准号: 7071765
• 负责人: JILL B. BECKER
• 金额: $ 28.56万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7071765
• 关键词: behavioral /social science research tag; behavioral habituation /sensitization; cocaine; corpus striatum; drug abuse; estrogens; gender difference; hormone regulation /control mechanism; laboratory rat; neurochemistry; nucleus accumbens; progesterone; self medication

DESCRIPTION (provided by applicant): The onset of addiction to cocaine is more rapid in women than in men. Women begin using cocaine earlier, enter treatment at earlier ages, and are taking more cocaine at intake than men. Furthermore, cocaine cues induce more drug craving in female than male addicts. Basic research on the role of sex and ovarian hormones in the neurochemical and behavioral responses to acute and repeated exposure to cocaine is an important next step to enhance our understanding of the processes involved in gender differences in drug abuse. Experiments proposed will test the hypothesis that female rats are more susceptible to the behavioral effects of cocaine than are males because of organizational effects of gonadal hormones during development as well as activational effects of estrogen in adulthood. As a first step towards determining if there are organizational effects of gonadal hormones during prenatal development, we will look at whether there are sex differences in adulthood independent of circulating gonadal hormones in behavioral and neurochemical responses to cocaine. We will also investigate whether estrogen in adult females further enhances the induction and persistence of these measures. Finally, we will explore whether treatment can ameliorate these sex differences, experiments will test the hypothesis that progesterone can reverse the effect of estrogen on cocaine self-administration. There are 5 specific aims which address these hypotheses: 1) To determine if there are sex differences in or hormonal influences on the persistence of behavioral sensitization to cocaine. 2) To determine if in females, estrogen enhances behavioral sensitization by potentiating the cocaine-stimulated increase in dopamine in dialysate from the dorsal striatum and nucleus accumbens acutely and after sensitization to cocaine. 3) To determine the effect of sex and gonadal hormones on reinstatement of cocaine self-administration. 4) To determine the effect of sex and gonadal hormones on acquisition of cocaine self-administration and breaking point after prior sensitization to cocaine. 5) To determine if progesterone can reverse the effects of estrogen on cocaine self-administration.

描述（由申请人提供）：女性对可卡因成瘾的发病速度比男性更快。女性比男性更早开始使用可卡因，更早开始接受治疗，并且摄入的可卡因更多。此外，与男性成瘾者相比，可卡因提示会引起女性成瘾者更多的药物渴望。关于性激素和卵巢激素在急性和反复接触可卡因的神经化学和行为反应中的作用的基础研究是加强我们对药物滥用性别差异过程的理解的重要下一步。 提出的实验将检验以下假设：由于发育过程中性腺激素的组织效应以及成年期雌激素的激活作用，雌性大鼠比雄性大鼠更容易受到可卡因的行为影响。作为确定性腺激素在产前发育过程中是否存在组织影响的第一步，我们将研究成年后对可卡因的行为和神经化学反应是否存在独立于循环性腺激素的性别差异。我们还将研究成年女性中的雌激素是否进一步增强这些措施的诱导和持久性。最后，我们将探讨治疗是否可以改善这些性别差异，实验将检验黄体酮可以逆转雌激素对可卡因自我给药的影响的假设。 针对这些假设有 5 个具体目标：1) 确定可卡因行为敏感性的持续性是否存在性别差异或激素影响。 2) 确定在女性中，雌激素是否通过增强可卡因刺激的背侧纹状体和伏隔核透析液中多巴胺的增加来增强行为敏感性，以及在对可卡因过敏后。 3) 确定性激素和性腺激素对恢复可卡因自我给药的影响。 4) 确定性激素和性腺激素对可卡因自我给药的获得和预先对可卡因致敏后的断裂点的影响。 5) 确定黄体酮是否可以逆转雌激素对可卡因自我给药的影响。