Neural Sensitivity to Stress During Drug Withdrawal

停药期间神经对压力的敏感性

基本信息

批准号：
8183906
负责人：
Gina L Forster
金额：
$ 24.5万
依托单位：
UNIVERSITY OF SOUTH DAKOTA
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-07-01 至 2016-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8183906
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

项目摘要

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. PUBLIC HEALTH RELEVANCE: Transition from amphetamine use to addiction may result, in part, from the need to alleviate dysphoric states, including heightened anxiety that emerge during drug abstinence. It is essential to understand the neurobiology underlying anxiety states during amphetamine withdrawal to identify potential pharmacotherapeutics, although very little research has been focused on this aspect of drug abuse. The current proposal will elucidate the neural mechanisms by which amphetamine withdrawal results heightened anxiety states and will test traditional and novel pharmacotherapies in a rat model of amphetamine withdrawal.

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。公共卫生相关性：从使用安非他明到成瘾的转变可能部分是由于需要缓解烦躁状态，包括戒毒期间出现的高度焦虑。尽管很少有研究关注药物滥用的这一方面，但了解安非他明戒断期间焦虑状态的神经生物学对于确定潜在的药物治疗至关重要。目前的提案将阐明安非他明戒断导致焦虑状态加剧的神经机制，并将在安非他明戒断大鼠模型中测试传统和新型药物疗法。