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.

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