Neural Sensitivity to Stress During Drug Withdrawal

停药期间神经对压力的敏感性

• 批准号: 6955271
• 负责人: Gina L Forster
• 金额: $ 24.15万
• 依托单位: UNIVERSITY OF SOUTH DAKOTA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6955271
• 关键词: amphetamines; anxiety; behavior test; behavioral /social science research tag; behavioral habituation /sensitization; central nervous system stimulants; coping; corticotropin releasing factor; craving; dorsal raphe nucleus; drug addiction; drug withdrawal; fluoxetine; high performance liquid chromatography; immunocytochemistry; laboratory rat; microdialysis; physiologic stressor; psychopharmacology; receptor expression; relapse /recurrence; serotonin receptor; substance abuse related behavior

DESCRIPTION (provided by applicant): Exposure to stressful events during withdrawal from psychostimulants, such as cocaine or amphetamine, induces drug craving and drug relapse in both animal models and human individuals. The effects of stress on drug-seeking behavior persist for months following psychostimulant abstinence, and play a large part in chronic relapses associated with psychostimulant addiction. It is the chronic nature of psychostimulant addiction and relapse that produces significant social, health and economic impact. Identifying the neurological alterations that occur during psychostimulant withdrawal will have significant impact on the development of pharmacological treatments designed to prevent drug relapse. The studies outlined by this proposal will determine whether psychostimulant abuse results in increased sensitivity of stress-related neural systems. These studies will also establish the duration of these effects during psychostimulant withdrawal. This will be achieved by using laboratory rat models of psychostimulant withdrawal. Changes in stress behavior, and alterations to the activity of neurotransmitter systems that regulate stress behavior, will be determined during acute and protracted withdrawal from amphetamine. Furthermore, studies will determine whether alterations to neural stress systems and stress behavior following psychostimulant withdrawal can be reversed by chronic treatment of the antidepressant, fluoxetine. Together, the proposed experiments will elucidate the neural substrates of stress sensitivity during psychostimulant withdrawal, and will determine the feasibility of antidepressant treatment to reduce stress behaviors and thus psychostimulant relapse.

描述（由申请人提供）：从可卡因或苯丙胺等精神刺激剂中退出时会暴露于压力事件，会在动物模型和人类的个体中引起药物渴望和药物复发。精神刺激性禁欲后，压力对毒品行为的影响持续数月，并且在与精神刺激成瘾有关的慢性复发中起着很大的作用。精神刺激成瘾和复发的长期性质产生了重大的社会，健康和经济影响。确定精神刺激性戒断期间发生的神经系统改变将对旨在防止药物复发的药理治疗的发展产生重大影响。该提案概述的研究将确定精神刺激滥用是否会导致与压力相关的神经系统的敏感性提高。这些研究还将确定精神刺激戒断期间这些影响的持续时间。这将通过使用精神刺激性戒断的实验室大鼠模型来实现。应力行为的变化以及调节压力行为的神经递质系统活性的改变，将在急性和持久退出苯丙胺中确定。此外，研究将确定对神经压力系统的改变和精神刺激性戒断后的压力行为是否可以通过长期治疗抗抑郁药氟西汀来逆转。共同提出的实验将阐明精神刺激性戒断期间压力敏感性的神经底物，并将确定抗抑郁治疗的可行性以减少压力行为，从而减少精神刺激性复发。