Gender differences in drug abuse

药物滥用的性别差异

• 批准号: 7857977
• 负责人: JILL B. BECKER
• 金额: $ 29万
• 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 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7857977
• 关键词: Acute; Addictive Behavior; Adolescence; Adolescent; Adult; Age; Androgens; Beer; Behavior; Behavioral; Brain; Characteristics; Cocaine; Cocaine Abuse; Corpus striatum structure; Dependence; Development; Disease; Dopamine; Drug abuse; Estradiol; Event; Exposure to; Female; Goals; Gonadal Hormones; Growth; Habits; Hormonal; Hormones; Human; Hypothalamic structure; Intake; Intervention; Mediating; Medical; Nucleus Accumbens; Outcome Measure; Ovarian hormone; Perinatal; Pharmaceutical Preparations; Pre-Clinical Model; Predisposition; Preoptic Areas; Process; Property; Psychological Factors; Rattus; Research; Rodent; Self Administration; Self-Administered; Sex Characteristics; Staging; Structure; Testing; Time; Treatment Protocols; Walkers; Woman; addiction; base; cocaine exposure; cocaine use; dopamine system; improved; male; men; neurotransmission; peripubertal period; primary outcome; relating to nervous system; research study; response; sex

DESCRIPTION (provided by applicant): Women begin using cocaine, enter treatment at earlier ages than men, and have more severe cocaine use at intake than men. Thus, women progress from initial use to dependence faster than men do. This "telescoping" effect reflects a briefer time course for the development of medical consequences and behavioral/psychological factors characteristic of a dependence disorder. The studies proposed are a fundamentally important first step towards understanding structure-function relations in the induction and expression of drug-taking behavior and the long-term consequences of this behavior in both males and females. In this proposal we seek to identify the hormonal and developmental events that produce a sexually dimorphic ascending dopamine system that results in sex differences in drug abuse liability, and to identify some of the associated neural processes that mediate these sex differences. There are two times during development of the brain when hormones can influence its organization. In the rat these occur during the peri-natal period and again during the peri-pubertal period. Experiments are proposed to test the hypothesis that the enhanced vulnerability of females for cocaine abuse is dependent on the lack of exposure to gonadal hormones during the critical perinatal period, as well as subsequent exposure to ovarian hormones during the peripubertal period. Self-administration of cocaine will be used as the primary outcome measure. Acquisition of drug taking behavior during adolescence in humans is a strong predictor of drug abuse problems as an adult. We hypothesize that onset of hormone exposure during the peri-pubertal period contributes to increased vulnerability for the reinforcing and/or long-term consequences of cocaine treatment in both males and females. We will determine whether adolescence is a period of enhanced vulnerability for female vs. male rats to self-administer cocaine. Alternatively, it is possible that adolescents aren't more vulnerable to the addictive properties of the psychomotor stimulants, but that the long-term consequences of exposure to these drugs during adolescence result in increased susceptibility as an adult, this possibility will be examined as well. Finally, the neural basis of the organizational and developmental influences on sex differences in the response to cocaine will be examined by looking at dopamine in dialysate from striatum and nucleus accumbens. These experiments are a first step towards exploring the extent that sex differences in vulnerability for cocaine abuse impacts the striatum and nucleus accumbens. Women are more vulnerable to becoming addicted to cocaine than are men. The experiments proposed will investigate the neurodevelopmental processes that contribute to this gender difference in drug abuse using a preclinical model. The long-term goal of this project is to develop better intervention and treatment protocols for both men and women based on an improved understanding of neural basis of vulnerability to addiction.

描述（由申请人提供）：女性开始使用可卡因，比男性更早开始接受治疗，并且在摄入可卡因时比男性更严重。因此，女性从最初使用到依赖的速度比男性更快。这种“伸缩”效应反映了依赖性障碍的医学后果和行为/心理因素特征的发展的更短的时间过程。所提出的研究是理解吸毒行为的诱导和表达的结构功能关系以及这种行为对男性和女性的长期后果至关重要的第一步。在本提案中，我们试图确定产生性别二态性上升多巴胺系统的激素和发育事件，从而导致药物滥用倾向的性别差异，并确定介导这些性别差异的一些相关神经过程。在大脑发育过程中，激素有两次会影响其组织。在大鼠中，这些发生在围产期和围青春期期间。提出实验来检验以下假设：女性对可卡因滥用的脆弱性增加取决于在关键的围产期期间缺乏性腺激素的暴露，以及随后在青春期期间缺乏卵巢激素的暴露。自我服用可卡因将被用作主要结果衡量标准。人类在青春期习得吸毒行为是成年后吸毒问题的有力预测因素。我们假设，在青春期前后开始接触激素会增加男性和女性对可卡因治疗的强化和/或长期后果的脆弱性。我们将确定青春期是否是雌性大鼠与雄性大鼠更容易自我注射可卡因的时期。或者，青少年可能并不更容易受到精神运动兴奋剂的成瘾特性，但青春期期间接触这些药物的长期后果会导致成年后的易感性增加，这种可能性也将得到检验。最后，将通过观察纹状体和伏隔核透析液中的多巴胺来检查可卡因反应中性别差异的组织和发育影响的神经基础。这些实验是探索可卡因滥用脆弱性的性别差异对纹状体和伏核的影响程度的第一步。女性比男性更容易对可卡因上瘾。拟议的实验将使用临床前模型研究导致药物滥用性别差异的神经发育过程。该项目的长期目标是在更好地了解成瘾脆弱性的神经基础的基础上，为男性和女性制定更好的干预和治疗方案。