Drug Abuse Vulnerability: Role of Development and Gender

药物滥用脆弱性：发展和性别的作用

• 批准号: 7049094
• 负责人: LISA M SCHROTT
• 金额: $ 25.06万
• 依托单位: LOUISIANA STATE UNIV HSC SHREVEPORT
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7049094
• 关键词: anxiety; child psychology; cocaine; cues; disease /disorder proneness /risk; drug abuse; drug withdrawal; early experience; embryo /fetus toxicology; gender difference; heroin; hypothalamic pituitary adrenal axis; laboratory rat; morphine; neurochemistry; neuropharmacology; neurotoxicology; newborn human (0-6 weeks); opiate alkaloid; pain threshold; reinforcer; self medication; substance abuse epidemiology; substance abuse related behavior

DESCRIPTION (provided by applicant): Developmental history and gender are thought to be key mediating factors in drug addiction, affecting initial drug use, escalation to abuse, and relapse. Developmental insults can affect structural and neurochemical elements that are directly involved in the reinforcing properties of drugs, or they can perturb systems that modulate the response to stressors and aversive stimuli and thus, indirectly affect drug use. With respect to addiction vulnerability, an understudied developmental insult is prenatal and early postnatal exposure to and withdrawal from drugs of abuse. This is particularly relevant for developmental opiate exposure. The Center for Substance Abuse Treatment recommends that opiate-dependent pregnant women be maintained on opiate substitution therapy throughout pregnancy to minimize the health risks to the mother and fetus that are associated with heroin use. In addition to the direct effects of opiate, a prolonged and stressful withdrawal from the opiates occurs in the neonate (abstinence syndrome), which can further act as a developmental insult. Numerous published studies have reported that gender influences the long-term consequences of developmental insults and preliminary studies have revealed that gender differentially affects the consequences of prenatal opiate exposure on measures of adult anxiety behavior and pain sensitivity. However, there has not been a systematic study of how prenatal drug exposure and the accompanying stress of postnatal opiate withdrawal, interact with gender to affect abuse liability in adulthood, the goal of this research proposal. Subjects will originate from female rats that are made dependent on a long-acting synthetic opiate one month prior to breeding, with treatment through parturition. After birth the pups will be fostered to drug-naive mothers and undergo opiate withdrawal. In adulthood, studies will determine if prenatal opiate exposed male and female rats have differential sensitivity to drug-induced activation and adaptation of the hypothalamic-pituitary-adrenal axis; opiate-withdrawal enhanced anxiety, pain sensitivity, and place aversion; and increased acquisition and cue-induced reinstatement of cocaine and heroin self-administration.

描述（由申请人提供）：发展史和性别被认为是药物成瘾的关键中介因素，影响最初的药物使用，升级到滥用和复发。发育损伤可以影响直接参与药物强化特性的结构和神经化学元素，或者它们可以扰乱调节对压力源和厌恶刺激的反应的系统，从而间接影响药物使用。关于成瘾脆弱性，一个未被充分研究的发育侮辱是产前和产后早期对药物滥用的暴露和戒断。这与发展性阿片类药物暴露特别相关。药物滥用治疗中心建议依赖阿片类药物的孕妇在整个怀孕期间继续使用阿片类药物替代疗法，以尽量减少与海洛因使用有关的对母亲和胎儿的健康风险。除了阿片类药物的直接影响外，长期和紧张的戒断阿片类药物会发生在新生儿身上（戒断综合征），这可能进一步成为发育的侮辱。许多已发表的研究报告称，性别影响发育损伤的长期后果，初步研究表明，性别差异影响产前阿片类药物暴露对成人焦虑行为和疼痛敏感性测量的后果。然而，目前还没有系统的研究表明，产前药物暴露和产后阿片类药物戒断的压力如何与性别相互作用，影响成年后的滥用倾向，这是本研究的目标。实验对象来自雌性大鼠，雌性大鼠在繁殖前一个月依赖于一种长效合成阿片类药物，并通过分娩进行治疗。出生后，幼崽将被培养给不吸毒的母亲，并接受阿片类药物的戒断。在成年期，研究将确定产前暴露于阿片类药物的雄性和雌性大鼠对药物诱导的下丘脑-垂体-肾上腺轴的激活和适应是否具有不同的敏感性；阿片类戒断增强焦虑、疼痛敏感性和地方厌恶；获得可卡因和海洛因的几率增加，并因暗示而恢复自我服用。