Addiction, Gender and Endocrine Disruptors

摘要 这一新项目是三个重要研究领域的结合体：吸毒、性 差异和环境健康。与毒品有关的行为的性别差异一直是 有充分的文献记载，并归因于雌激素和黄体酮在成年女性中的作用。 在这里，我们超越了这个假设，检查了另外两个因素，这两个因素都有 通过他们对多巴胺系统的作用被牵连到奖励中。内分泌干扰物 (内分泌细胞)普遍存在于环境中，已知可以改变大脑和大脑中的性别差异 行为。当EDC发生在新生儿发育期间时，接触EDC尤其有效。 因此，它是成人疾病胎儿起源的模型。这笔为期两年的拨款将考验 假设暴露于双酚A(BPA)，一种研究得很好和丰富的内分泌细胞 在环境中，会增加对可卡因的易感性。进一步剖析性别的作用 在药物易感性方面，将使用四个核心基因(FCG)小鼠模型。FCG 允许单独分析性腺激素和性染色体组成(XX与XY)。 在目标一中，将在怀孕期间接触双酚A进行剂量-反应研究。在……里面 下一个目标是对FCG小鼠进行测试。成年小鼠颈静脉慢性留置 可以让他们自我注射可卡因的插管。固定比率表和累进比率表 用于检查自我管理并衡量购置和维护。这个 这项工作的长期目标是制定一项研究计划，以测试 环境内分泌干扰化合物与性别的结合，关于动机 寻毒、吸食毒品行为。

Abstract This new program is a marriage of three important research fields; Drug Addiction, Sex Differences, and Environmental Health. Sex differences in drug-related behaviors have been well documented and attributed to actions of estrogens and progesterone in adult females. Here we move beyond this hypothesis and examine two other factors both of which have been implicated in reward via their actions on the dopamine system. Endocrine disruptors (EDCs) are ubiquitous in the environment and are known to alter sex differences in brain and behavior. EDC exposure is particularly potent when it occurs during neonatal development. As such it is a model for fetal origins of adult disease. This two-year grant will test the hypothesis that exposure to Bisphenol A (BPA), one of the well-studied and abundant EDCs in the environment, can increase vulnerability to cocaine. To further dissect the role of gender on drug vulnerability the four core genotype (FCG) mouse model will be used. The FCG allows separate analysis of gonadal hormones and sex chromosome complement (XX vs. XY). In aim one a dose-response study will be conducted with BPA exposure during gestation. In the next aim the FCG mice will be tested. Adult mice are fitted with chronic indwelling jugular cannula which allow them to self-administer cocaine. Fixed and progressive ratio schedules are used to examine self-administration and measure both acquisition and maintenance. The long term objectives of this work are to develop a research program to test the effects of environmental endocrine disrupting compounds in combination with gender, on motivated drug seeking and taking behavior.