DOES EXERCISE AMELIORATE THE EFFECTS OF EARLY LIFE STRESS ON DRUG REWARD?

锻炼是否可以改善早期生活压力对药物奖赏的影响？

• 批准号: 8360617
• 负责人: Laurel Pritchard
• 金额: $ 9.2万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360617
• 关键词: Adolescence; Adult; Behavior Therapy; Behavioral; Biomedical Research; Brain region; Brain-Derived Neurotrophic Factor; Child Abuse and Neglect; Chronic stress; Cocaine; Development; Drug abuse; Exercise; Funding; Goals; Grant; Housing; Individual; Injection of therapeutic agent; Intervention; Life Stress; Measures; Modeling; National Center for Research Resources; Neonatal; Outcome; Pharmaceutical Preparations; Physical activity; Principal Investigator; Proteins; Rattus; Research; Research Infrastructure; Resources; Running; Source; Stress; Substance Addiction; Substance abuse problem; Survivors; Testing; Time; United States National Institutes of Health; Weaning; base; cocaine exposure; cohort; cost; dopamine transporter; drug reward; high risk; maternal separation; neuroadaptation; novel; pediatric trauma; postnatal; preference; prevent; psychostimulant; relating to nervous system; research study; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The long-term objective of our research is to better understand the neural underpinnings of enhanced vulnerability to substance abuse and dependence in survivors of childhood maltreatment and trauma. The goal of this project is to examine the effects of a specific intervention  voluntary exercise  on behavioral responses and neural adaptations to psychostimulant drugs in a rat model of early life stress. Our central hypothesis is that voluntary exercise during adolescence will normalize the altered psychostimulant sensitivity previously observed in rats exposed to chronic stress during early postnatal development. Neonatal maternal separation, a rat model of early life stress, is known to produce stress hyper-responsiveness and enhanced sensitivity to psychostimulants that persist into adulthood. Starting at the time of weaning, we will house previously-separated rats and briefly handled controls in cages with or without access to running wheels for three weeks. After the three-week exercise manipulation, we will carry out two experiments with separate cohorts of rats. In experiment 1, we will test rats for their sensitivity to the psychomotor stimulant and reinforcing effects of cocaine in a conditioned-place preference paradigm. In experiment 2, we will test rats for psychomotor sensitization after repeated cocaine injection. We will also measure expression of the dopamine transporter (DAT) and brain-derived neurotrophic factor (BDNF) in limbic brain regions implicated in drug abuse. These proteins were chosen because both are regulated in limbic brain regions by maternal separation and repeated cocaine exposure. We expect that regular exercise will normalize the altered psychostimulant sensitivity and associated neural adaptations induced by maternal separation. The proposed studies will enhance understanding of the mechanisms by which early life stress and physical activity interact to impact substance abuse vulnerability. The outcomes could provide the scientific basis for novel behavioral interventions to prevent or reduce substance abuse in high-risk individuals.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 我们研究的长期目的是更好地了解儿童虐待和创伤幸存者对药物滥用和依赖的脆弱性的神经基础。该项目的目的是研究特定干预措施对行为反应和神经适应精神刺激药物的影响，在早期生活压力的大鼠模型中。我们的中心假设是，在青春期期间的自愿运动将使先前在出生后早期发育期间暴露于慢性应激的大鼠中观察到的精神刺激敏感性改变。 已知新生儿母体分离是一种早期生命压力的大鼠模型，会产生压力超反应性，并增强对持续成年的精神刺激物的敏感性。从断奶开始时，我们将容纳先前分离的大鼠，并在笼子中短暂处理控制，无论有或不使用跑步轮三个星期。经过为期三周的运动操作后，我们将进行两次单独的大鼠同志的实验。在实验1中，我们将测试大鼠对可卡因在条件地位偏好范式中可卡因的刺激性和增强作用的敏感性。在实验2中，我们将在重复可卡因注射后测试大鼠的精神运动敏化。我们还将测量与药物滥用有关的边缘脑区域中多巴胺转运蛋白（DAT）和脑衍生的神经营养因子（BDNF）的表达。之所以选择这些蛋白质，是因为两者都通过母体分离和重复的可卡因暴露在边缘大脑区域进行调节。 我们预计定期运动将使孕产妇分离引起的精神刺激敏感性改变和相关的神经适应性变化。拟议的研究将增强对早期生活压力和体育锻炼相互作用以影响药物滥用脆弱性的机制的理解。结果可以为新型行为干预措施提供科学基础，以防止或减少高危个人的滥用药物。