Drug Abuse Vulnerability: Role of Development and Gender

发展史和性别被认为是吸毒成瘾的关键中介因素，影响 初次吸毒，升级为滥用，以及复发。发育性侮辱会影响结构性和 直接参与药物增强特性的神经化学元素，或者它们可以 干扰系统，调节对应激源和厌恶刺激的反应，从而间接影响 吸毒。关于成瘾易感性，一种未被研究的发育侮辱是产前和 出生后早期接触和戒除滥用药物。这与以下方面尤其相关 发育性阿片类药物暴露。药物滥用治疗中心建议 阿片依赖孕妇在整个怀孕期间继续接受阿片替代治疗 尽量减少与海洛因使用有关的母亲和胎儿的健康风险。除 鸦片类药物的直接作用，即长期和有压力地戒断鸦片类药物会发生在新生儿身上。 (禁欲综合症)，这可能进一步成为对发育的侮辱。众多已发表的研究 报告称，性别会影响发育侮辱的长期后果， 初步研究表明，性别差异会影响产前鸦片类药物的后果。 暴露在成人焦虑行为和疼痛敏感度的测量上。然而，还没有一个 产前药物暴露与产后阿片类药物伴随应激的系统研究 退缩、与性别的互动影响成年后的虐待倾向，是本研究建议的目标。 受试者将来自对长效合成鸦片类药物依赖的雌性大鼠 在生育前一个月，通过分娩进行治疗。出生后，幼崽将被寄养到 毒品天真的母亲和经历阿片类药物戒断。在成年期，研究将确定产前鸦片是否 暴露的雄性和雌性大鼠对药物诱导的激活和适应具有不同的敏感性 下丘脑-垂体-肾上腺轴；阿片类药物戒断增强焦虑、疼痛敏感性和部位 厌恶；以及更多的可卡因和海洛因的获得和线索诱导的恢复 自治。

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 stressfulwithdrawal from the opiates occurs in the neonate (abstinence syndrome), which can further act as a developmental insult. Numerous published studies have reportedthat 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.