Gender Differences in Drug Abuse

药物滥用的性别差异

• 批准号: 6688005
• 负责人: JILL B. BECKER
• 金额: $ 29.19万
• 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/6688005
• 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)：女性对可卡因的上瘾比男性更快。女性开始使用可卡因的时间更早，接受治疗的年龄更早，而且在摄入可卡因时比男性服用的可卡因更多。此外，可卡因线索使女性比男性吸毒者更容易产生毒瘾。对性激素和卵巢激素在急性和反复暴露可卡因的神经化学和行为反应中的作用进行基础研究，是下一步加强我们对药物滥用性别差异过程的理解的重要下一步。 提出的实验将检验一种假设，即雌性大鼠比雄性大鼠更容易受到可卡因的行为影响，这是因为性腺激素在发育过程中的组织效应，以及成年后雌激素的激活效应。作为确定性腺激素在产前发育过程中是否存在组织效应的第一步，我们将研究成年期是否存在性别差异，而不是循环性腺激素对可卡因的行为和神经化学反应。我们还将调查成年女性体内的雌激素是否进一步增强了这些措施的诱导性和持久性。最后，我们将探索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。 有5个具体的目标来解决这些假说：1)确定是否存在性别差异或激素对可卡因的行为敏感化持久性的影响。2)为了确定雌激素是否通过增强可卡因刺激的背侧纹状体和伏核透析液中多巴胺的增加以及可卡因增敏后，在女性中增强了行为敏感化。3)研究性激素和性腺激素对可卡因恢复给药的影响。4)研究性激素和性腺激素对可卡因自身给药和预先致敏后的断裂点的影响。5)确定孕酮能否逆转雌激素对可卡因自身给药的影响。