Neural Sensitivity to Stress During Drug Withdrawal

停药期间神经对压力的敏感性

• 批准号: 7242503
• 负责人: Gina L Forster
• 金额: $ 22.85万
• 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/7242503
• 关键词: Abstinence; Acute; Amphetamines; Animal Model; Antidepressive Agents; Anxiety; Behavior; Cells; Chronic; Cocaine; Corticotropin-Releasing Hormone; Development; Dorsal; Equilibrium; Exposure to; Fluoxetine; Human; Individual; Laboratory Rat; Medial; Mediating; Microdialysis; Modeling; Nature; Neurologic; Neurotransmitters; Output; Pharmacological Treatment; Play; Prefrontal Cortex; Production; Psychostimulant dependence; Rattus; Relapse; Role; Serotonin; Site; Staging; Stress; Stressful Event; System; Techniques; Testing; Withdrawal; biological adaptation to stress; density; dorsal raphe nucleus; drug craving; drug relapse; drug seeking behavior; drug withdrawal; health economics; immunocytochemistry; in vivo; inhibitor/antagonist; prevent; psychostimulant; raphe nuclei; receptor; relating to nervous system; research study; reuptake; social; stimulant abuse; therapy design

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）：在动物模型和人类个体中，在戒除可卡因或安非他明等精神兴奋剂期间暴露于压力事件会诱发药物渴望和药物复发。精神兴奋剂戒断后，压力对吸毒行为的影响持续数月，并且在与精神兴奋剂成瘾相关的慢性复发中发挥着重要作用。精神兴奋剂成瘾和复发的慢性性质会产生重大的社会、健康和经济影响。识别精神兴奋剂戒断期间发生的神经学改变将对旨在预防药物复发的药物治疗的开发产生重大影响。该提案概述的研究将确定精神兴奋剂滥用是否会导致与压力相关的神经系统的敏感性增加。这些研究还将确定精神兴奋剂戒断期间这些影响的持续时间。这将通过使用精神兴奋剂戒断的实验室大鼠模型来实现。应激行为的变化以及调节应激行为的神经递质系统活动的改变将在急性和长期戒断安非他明期间确定。此外，研究将确定精神兴奋剂戒断后神经应激系统和应激行为的改变是否可以通过抗抑郁药氟西汀的长期治疗来逆转。总之，所提出的实验将阐明精神兴奋剂戒断期间压力敏感性的神经基础，并将确定抗抑郁治疗以减少压力行为和精神兴奋剂复发的可行性。