Amygdala Neurons and Cocaine

杏仁核神经元和可卡因

• 批准号: 7082967
• 负责人: PATRICIA SHINNICK-GALLAGHER
• 金额: $ 29.49万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 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/7082967
• 关键词: amygdala; behavioral /social science research tag; biological signal transduction; cocaine; cues; dopamine; dopamine receptor; drug withdrawal; electrodes; electrophysiology; glutamate receptor; glutamates; laboratory rat; long term potentiation; neural information processing; neural plasticity; neural transmission; neuropharmacology; synapses; voltage /patch clamp; western blottings

DESCRIPTION (provided by applicant): The amygdala, part of the brain reward circuitry, plays a role in cocaine-seeking and withdrawal in animals and craving and relapse in humans. The incentive motivation for cocaine is associated with cocaine cues and the amygdala is essential in forming drug-related associations. The membrane effects of chronic cocaine on amygdala neurons, however, are not known and mechanisms underlying drug-related associations are only beginning to be understood. The long-term objective of this research is to analyze the mechanisms underlying cocaine cue-related information by characterizing the modulation and modification of amygdala neurotransmission at the synaptic level during withdrawal from chronic cocaine. Chronic cocaine enhances glutamatergic transmission and group I metabotropic glutamate receptor (mGluR) effects in amygdala neurons. Dopamine also plays a role in cue related events in the amygdala. The proposed experiments will test the hypothesis that 2 weeks after withdrawal from chronic cocaine persistent alterations of neurotransmission and plasticity are specific for amygdala pathways and modulated by metabotropic glutamate and dopaminergic receptors. In these experiments synaptic transmission in intra-amygdala pathways is recorded using sharp electrode, whole cell patch, and extracellular recording in amygdala slices. The overall goal is to analyze membrane measures of cue-associated cocaine memory after chronic cocaine withdrawal, specifically: 1. Characterize the modifications in glutamatergic synaptic transmission and plasticity to stimuli representing drug-related cues and determine the underlying signaling mechanisms during chronic cocaine withdrawal; 2. Analyze the role of metabotropic glutamate and dopamine receptors in modulating synaptic transmission and plasticity and determine the underlying signaling mechanisms after withdrawal from chronic cocaine. These studies will determine synaptic mechanisms underlying neuroadaptations and intra-amygdala communication of drug-related cues after chronic cocaine withdrawal and may lead to novel and more rational strategies to block cue-induced relapse of cocaine addiction.

描述（由申请人提供）：杏仁核是大脑奖励回路的一部分，在动物的可卡因寻求和戒断以及人类的渴望和复发中发挥着作用。可卡因的激励动机与可卡因线索有关，而杏仁核对于形成与毒品相关的关联至关重要。然而，慢性可卡因对杏仁核神经元的膜效应尚不清楚，药物相关关联的机制才刚刚开始被了解。这项研究的长期目标是通过表征长期可卡因戒断期间突触水平杏仁核神经传递的调节和修饰来分析可卡因线索相关信息的潜在机制。慢性可卡因增强杏仁核神经元中的谷氨酸能传递和 I 类代谢型谷氨酸受体 (mGluR) 作用。多巴胺还在杏仁核中与线索相关的事件中发挥作用。拟议的实验将检验这样的假设：长期戒除可卡因后两周，神经传递和可塑性的持续改变是杏仁核通路特有的，并受到代谢型谷氨酸和多巴胺能受体的调节。在这些实验中，使用尖锐电极、全细胞贴片和杏仁核切片中的细胞外记录来记录杏仁核内通路中的突触传递。总体目标是分析慢性可卡因戒断后与线索相关的可卡因记忆的膜测量，具体来说： 1. 表征谷氨酸突触传递的变化和对代表药物相关线索的刺激的可塑性，并确定慢性可卡因戒断期间潜在的信号传导机制； 2. 分析代谢型谷氨酸和多巴胺受体在调节突触传递和可塑性中的作用，并确定长期可卡因戒断后潜在的信号传导机制。这些研究将确定慢性可卡因戒断后神经适应和杏仁核内药物相关线索通讯的突触机制，并可能导致新的、更合理的策略来阻止线索诱导的可卡因成瘾复发。