Lipase in Cocaine Cue Associations in the Amygdala

杏仁核中可卡因提示关联中的脂肪酶

基本信息

批准号：
7850015
负责人：
BALAJI KRISHNAN
金额：
$ 5.89万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-04-18 至 2010-04-17
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7850015
关键词：
Abstinence Address Agonist American Amygdaloid structure Animal Model Animals Anxiety Area Association Learning Behavior Behavioral Brain Brain Part Cannulas Cessation of life Chronic Cocaine Cocaine Abuse Cocaine Dependence Coupled Cues Cysteine Data Drug Addiction Drug usage Emotional Environment Exhibits Exposure to Fright Glutamates Goals Health Human Implant Intake Laboratories Lead Learning Limbic System Link Lipase Long-Term Potentiation Measures Mediating Memory Metabotropic Glutamate Receptors Modeling Modification Names Neuronal Plasticity Neurons PCCG-13 Pathway interactions Pharmaceutical Preparations Phosphatidic Acid Phospholipase D Play Relapse Reporting Research Role Saline Signal Transduction Simulate Site Slice Structure Synapses Synaptic Transmission Synaptic plasticity System Testing Tetanus Texas Vesicle Withdrawal addiction classical conditioning cocaine use conditioned fear craving cysteine sulfinic acid dysphoria enzyme activity negative emotional state neurochemistry preference response reward circuitry success trafficking transmission process

项目摘要

DESCRIPTION (provided by applicant): Drug addiction is a significant health problem nationally and locally. Texas was named as one of 2 sites with highest rate of cocaine-related deaths from 2003 to 2004. In 2004, 34.2 million Americans (12 and over) reported lifetime use of cocaine. Thus treatment of addiction to cocaine is a national health issue. Cocaine craving and relapse to cocaine abuse is a feature of addiction that has devastating consequences even after long periods of abstinence. Factors that trigger this relapse include the presence of drug, drug paraphenalia, or environment associated with previous use of the drug. A brain area implicated in cuebased drug associative behavior is the amygdala. Since cues can trigger craving after long periods of abstinence, long-term changes in neuronal plasticity due to chronic cocaine use are likely. These changes may include the strengthening of certain synapses which may underlie the association between the drug and the context or environment in which drug-taking occurred. Such modifications can be mediated through changes in glutamatergic transmission similar to learning and memory mechanisms. Understanding the mechanisms contributing to the lasting association between the cues and cocaine administration is extremely valuable information since data will be directly applicable to treatments that will focus on targeting mechanisms underlying cocaine-craving and cocaine-associative behaviors. These studies would ultimately provide information that contributes to therapies which produce significantly higher success rates in treating cocaine addiction. Conditioned place preference (CPP) is an animal model measuring cue-induced cocaine associative behavior. We have shown that the activity of the enzyme, phospholipase D (PLD), is increased in the amygdala after cocaine-induced conditioned place preference. The overall goal of the proposed research is to determine the role of PLD in the synaptic changes that occur in cue-induced cocaine associative behavior during withdrawal from chronic cocaine. Two specific aims address this goal: specific aim 1, to characterize the role of amygdala PLD activity and mGluR-linked PLD in CPP and specific aim 2, to determine the mechanism by which the mGluR-linked PLD causes an increase in synaptic strength in the basolateral to central amygdala pathway. In this proposal, I plan to utilize behavioral, electrophysiological, and neurochemical approaches to study glutamatergic transmission in the amygdala of animals exhibiting CPP and undergoing 2 week withdrawal from chronic cocaine administration.

描述（由申请人提供）：吸毒成瘾是全国和地方的一个重大健康问题。德克萨斯州被评为 2003 年至 2004 年可卡因相关死亡率最高的两个地区之一。2004 年，有 3,420 万美国人（12 岁及以上）报告称终生使用可卡因。因此，治疗可卡因成瘾是一个全国性的健康问题。对可卡因的渴望和复发可卡因滥用是成瘾的一个特征，即使在长期戒断后也会产生毁灭性的后果。引发这种复发的因素包括药物的存在、药物用具或与先前使用药物相关的环境。与基于提示的药物关联行为有关的大脑区域是杏仁核。由于长期戒断后的暗示可能会引发渴望，因此长期使用可卡因可能会导致神经元可塑性发生长期变化。这些变化可能包括某些突触的加强，这些突触可能是药物与吸毒发生的背景或环境之间关联的基础。这种修饰可以通过类似于学习和记忆机制的谷氨酸传递的变化来介导。了解线索与可卡因服用之间持久关联的机制是非常有价值的信息，因为数据将直接适用于专注于可卡因渴望和可卡因相关行为背后的机制的治疗。这些研究最终将提供有助于治疗可卡因成瘾的疗法的信息，从而显着提高治疗可卡因成瘾的成功率。条件性位置偏好（CPP）是一种测量线索诱导的可卡因联想行为的动物模型。我们已经证明，在可卡因诱导条件性位置偏好后，杏仁核中磷脂酶 D (PLD) 的活性增加。本研究的总体目标是确定 PLD 在长期可卡因戒断期间提示诱发的可卡因联想行为中发生的突触变化中的作用。两个具体目标解决了这一目标：具体目标 1，表征杏仁核 PLD 活性和 mGluR 连接的 PLD 在 CPP 中的作用，具体目标 2，确定 mGluR 连接的 PLD 导致 CPP 中突触强度增加的机制。基底外侧至中央杏仁核通路。在本提案中，我计划利用行为、电生理学和神经化学方法来研究表现出 CPP 并经历长期可卡因戒断 2 周的动物杏仁核中的谷氨酸传递。