Amygdala Neurons and Cocaine

杏仁核神经元和可卡因

• 批准号: 8043304
• 负责人: Jie Liu
• 金额: $ 29.79万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 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 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8043304
• 关键词: Abstinence; Amygdaloid structure; Animals; Area; Behavior; Brain; Brain Part; Cell Nucleus; Cells; Characteristics; Chronic; Cocaine; Cocaine Dependence; Communication; Control Animal; Cues; Dopamine; Dopamine Antagonists; Dopamine Receptor; Electrodes; Event; Extinction (Psychology); Frequencies; Glutamates; Goals; Human; In Vitro; Incentives; Lateral; Lead; Learning; Long-Term Potentiation; Measures; Membrane; Memory; Metabotropic Glutamate Receptors; Modification; Motivation; Neurons; Output; Pathway interactions; Pharmaceutical Preparations; Play; Property; Proteins; Receptor Signaling; Relapse; Research; Research Personnel; Resistance; Role; Self Administration; Signal Transduction; Slice; Stimulus; Synapses; Synaptic Transmission; Synaptic plasticity; Testing; Western Blotting; Withdrawal; craving; extracellular; in vivo; insight; neuroadaptation; neurotransmission; novel; programs; receptor; relating to nervous system; research study; response; reward circuitry; transmission process

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）：杏仁核是大脑奖励电路的一部分，在动物的可卡因寻求和戒断中发挥作用，人类的渴望和复发。可卡因的激励动机与可卡因提示有关，杏仁核对于形成与药物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作用尚不清楚，与药物相关关联的基础机制刚刚开始被理解。这项研究的长期目标是通过表征从慢性可卡因撤离期间在突触水平上的调节和修饰可卡因提示相关信息的基础机制。慢性可卡因可增强谷氨酸能传播和I组代谢性谷氨酸受体（MGLUR）在杏仁核神经元中的作用。多巴胺在杏仁核中还起着与提示相关的事件的作用。提出的实验将检验以下假设：从慢性可卡因撤离后2周，神经传递和可塑性的持续改变是特定于杏仁核途径，并通过代谢型谷氨酸和多巴胺能受体调节。在这些实验中，使用尖锐的电极，全细胞贴片和杏仁核切片中的细胞外记录记录了杏仁核内途径中的突触传播。总体目标是分析慢性可卡因戒断后与可卡因相关的可卡因记忆的膜测量，特别是： 1。表征谷氨酸能突触传递和可塑性的修饰，以刺激代表药物相关的提示，并确定慢性可卡因戒断期间的基本信号传导机制； 2。分析代谢剂谷氨酸和多巴胺受体在调节突触传播和可塑性中的作用，并确定从慢性可卡因退出后的基本信号传导机制。这些研究将确定神经适应的基础突触机制和慢性可卡因戒断后药物相关提示的杏仁核内通信，并可能导致新的和更合理的策略，以阻止可卡因成瘾的提示引起的提示诱导的可卡因复发。

项目成果

Dopamine receptor mechanisms mediate corticotropin-releasing factor-induced long-term potentiation in the rat amygdala following cocaine withdrawal.

• DOI: 10.1111/j.1460-9568.2010.07148.x
• 发表时间: 2010-03
• 期刊: The European journal of neuroscience
• 作者: Krishnan B;Centeno M;Pollandt S;Fu Y;Genzer K;Liu J;Gallagher JP;Shinnick-Gallagher P
• 通讯作者: Shinnick-Gallagher P

Cocaine withdrawal reduces group I mGluR-mediated long-term potentiation via decreased GABAergic transmission in the amygdala.

• DOI: 10.1111/j.1460-9568.2011.07769.x
• 发表时间: 2011-07
• 期刊: The European journal of neuroscience
• 作者: Schmidt K;Krishnan B;Xia Y;Sun A;Orozco-Cabal L;Pollandt S;Centeno M;Genzer K;Gallagher JP;Shinnick-Gallagher P;Liu J
• 通讯作者: Liu J

Dopamine-induced plasticity, phospholipase D (PLD) activity and cocaine-cue behavior depend on PLD-linked metabotropic glutamate receptors in amygdala.

• DOI: 10.1371/journal.pone.0025639
• 发表时间: 2011
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Krishnan B;Genzer KM;Pollandt SW;Liu J;Gallagher JP;Shinnick-Gallagher P
• 通讯作者: Shinnick-Gallagher P