Addiction, Gender and Endocrine Disruptors

成瘾、性别和内分泌干扰物

基本信息

批准号：
9333775
负责人：
Wendy Jean Lynch
金额：
$ 20.34万
依托单位：
NORTH CAROLINA STATE UNIVERSITY RALEIGH
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-01 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9333775
关键词：
Address Adult Adult Children Age Barker Hypothesis Behavior Birth Brain region Cannulas Cannulations Cell Line Cells Centers for Disease Control and Prevention (U.S.)Chronic Cocaine Cocaine Dependence Deodorants Development Diet Dissection Dopamine Dose Drug Addiction Drug Exposure Ejaculation Embryo Endocrine Disruptors Environment Environmental Health Estrogens Ethnic Origin Evaluation Exposure to Female Funding Future Gender Genes Genetic Genotype Gonadal Hormones Grant Hormones Household Products Human Injury Laboratories Maintenance Marriage Measurable Measures Messenger RNA Midbrain structure Milk Modeling Motivation Mus Neonatal Neurons No-Observed-Adverse-Effect Level Operative Surgical Procedures Partner in relationship Persons Pharmaceutical Preparations Physiology Phytoestrogens Ploidies Polychlorinated Biphenyls Postdoctoral Fellow Pregnancy Progesterone Publications Rattus Recruitment Activity Research Rewards Role Schedule Self Administration Self-Administered Sex Characteristics Sex Chromosomes Social Behavior Statistical Data Interpretation Substantia nigra structure Testing Testis Tyrosine 3-Monooxygenase Universities Virginia Woman Work addiction bisphenol A brain behavior career clay dopamine system dopaminergic neuron endocrine disruptor exposure estrogenic fetal human male male man men mouse model phthalates pill programs response sex soft drink virtual

项目摘要

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.

抽象的这个新计划是三个重要研究领域的婚姻。吸毒成瘾，性差异和环境健康。与药物有关的行为的性别差异已经有据可查，并归因于成年女性中雌激素和孕激素的作用。在这里，我们超越了这一假设，并研究了其他两个因素通过他们对多巴胺系统的行动与奖励有关。内分泌破坏者（EDC）在环境中无处不在，众所周知会改变大脑的性别差异行为。在新生儿发育期间发生EDC暴露尤其有效。因此，它是成人疾病的胎儿起源的模型。这项为期两年的赠款将测试假设暴露于双酚A（BPA），这是一个良好且丰富的EDC之一在环境中，可以增加对可卡因的脆弱性。进一步剖析性别的作用在药物脆弱性上，将使用四种核心基因型（FCG）小鼠模型。 FCG 可以单独分析性腺激素和性染色体补体（XX与XY）。在妊娠期间，将对BPA暴露进行剂量反应研究。在下一个目标将测试FCG小鼠。成年小鼠装有慢性留置颈使他们能够自我管理可卡因的套管。固定比率时间表用于检查自我管理并衡量获取和维护。这这项工作的长期目标是制定研究计划，以测试环境内分泌破坏化合物与性别相结合，有动力寻求和服用行为的药物。