Neural Sensitivity to Stress During Drug Withdrawal

停药期间神经对压力的敏感性

• 批准号: 8482440
• 负责人: Gina L Forster
• 金额: $ 1.34万
• 依托单位: UNIVERSITY OF SOUTH DAKOTA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8482440
• 关键词: Abstinence; Address; Affect; Amphetamine Abuse; Amphetamines; Amygdaloid structure; Animal Model; Anxiety; Area; Attenuated; Behavior; Behavioral; Body Regions; Brain; Brain region; Cell Nucleus; Chronic; Complement; Corticosterone; Corticotropin-Releasing Hormone; Detection; Development; Disease; Drug Addiction; Drug abuse; Endocrine; Excision; Fright; Functional disorder; Glucocorticoid Receptor; Goals; Hippocampus (Brain); Hour; Human; Illicit Drugs; Infusion procedures; Long-Term Effects; Marijuana Abuse; Measures; Medial; Mediating; Mental Depression; Methamphetamine; Modeling; Neurobiology; Neurologic; Neuropeptides; Organic Cation Transporter; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacotherapy; Prefrontal Cortex; Prothrombin; Rattus; Relapse; Research; Serotonin; Signal Transduction; Stress; Substance Withdrawal Syndrome; System; Testing; Time; Tissues; Up-Regulation; Withdrawal; Withdrawal Symptom; World Health Organization; addiction; dorsal raphe nucleus; drug abstinence; drug craving; drug relapse; drug withdrawal; extracellular; neuroadaptation; neuromechanism; neuronal cell body; neurotransmission; novel; prevent; protein function; psychologic; psychostimulant; receptor; receptor expression; relating to nervous system; research study; response; serotonin transporter; stressor; therapy design; transmission process; urocortin II

DESCRIPTION (provided by applicant): The World Health Organization identifies methamphetamine as the second most widely abused illicit drug after marijuana, and abuse of prescription amphetamines in the US is increasing. Drug addiction is a chronic and relapsing disorder, and relapse is thought to arise, in part, from the need to alleviate negative withdrawal symptoms such as anxiety and depression. Amphetamine abuse is associated with a withdrawal syndrome that includes increased anxiety states during drug abstinence. We have developed a rat model of heightened anxiety during amphetamine withdrawal and have identified changes in serotonergic neurotransmission within several key limbic brain areas that are important for fear, anxiety and stress states. The goal of the current proposal is to elucidate the mechanisms by which amphetamine withdrawal results in altered serotonergic neurotransmission, and directly relate these to heightened anxiety states and stress sensitivity during withdrawal. Furthermore this proposal will test traditional and novel pharmacotherapies in this rat model of amphetamine withdrawal, to determine whether normalizing serotonergic function in the brain reverses heightened anxiety states that are observed during abstinence from amphetamine.

描述（由申请人提供）：世界卫生组织将甲基苯丙胺确定为仅次于大麻的第二大滥用的非法药物，并且美国处方苯丙胺的滥用正在增加。毒瘾是一种慢性、复发性疾病，人们认为复发的部分原因是需要缓解焦虑和抑郁等负面戒断症状。安非他明滥用与戒断综合症有关，包括戒毒期间焦虑状态增加。我们开发了一种在安非他明戒断期间焦虑加剧的大鼠模型，并确定了几个关键边缘大脑区域内血清素能神经传递的变化，这些变化对于恐惧、焦虑和压力状态很重要。当前提案的目标是阐明安非他明戒断导致血清素能神经传递改变的机制，并将这些机制与戒断期间焦虑状态和压力敏感性的升高直接相关。此外，该提案将在安非他明戒断大鼠模型中测试传统和新型药物疗法，以确定大脑中血清素能功能的正常化是否可以逆转安非他明戒断期间观察到的高度焦虑状态。