Drug Abuse Vulnerability: Role of Development and Gender

发展历史和性别被认为是药物成瘾的关键中介因素，影响 首次吸毒、滥用升级和复发。发育损伤会影响结构和 神经化学元素，直接参与药物的增强特性，或者它们可以 干扰系统，调节对压力源和厌恶刺激的反应，从而间接影响 吸毒关于成瘾的脆弱性，一个未充分研究的发展侮辱是产前， 出生后早期接触和戒断药物滥用。这一点尤其适用于 发育期的鸦片暴露药物滥用治疗中心建议， 阿片类药物依赖孕妇在整个怀孕期间应继续接受阿片类药物替代疗法， 尽量减少与使用海洛因有关的母亲和胎儿的健康风险。除了有 阿片类药物的直接作用，新生儿会出现长时间和应激性的阿片类药物戒断 （禁欲综合症），其可进一步充当发育性侮辱。许多已发表的研究 曾报道，性别影响发展性侮辱的长期后果， 初步研究表明，性别对产前阿片类药物的影响不同， 暴露对成人焦虑行为和疼痛敏感性的影响。然而，没有一个 系统研究产前药物暴露和产后阿片类药物的伴随压力 戒断，与性别交互影响成年期的虐待倾向，本研究的目标建议。 受试者将来自雌性大鼠，这些大鼠依赖于长效合成阿片类药物 在繁殖前一个月，通过分娩进行治疗。出生后，幼崽将被寄养在 未吸毒的母亲和经历阿片类药物戒断。在成年期，研究将确定是否产前阿片类药物 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、疼痛敏感性和位置 厌恶;可卡因和海洛因的获得和线索诱导的复吸增加 自我管理。

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 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.