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.