Amygdala Neurons and Cocaine

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作用。可卡因的刺激动机与可卡因线索有关，杏仁核在形成与毒品有关的联系方面至关重要。然而，慢性可卡因对杏仁核神经元的膜效应尚不清楚，与药物相关的潜在机制才刚刚开始被理解。本研究的长期目标是通过表征慢性可卡因戒断过程中杏仁核神经传递在突触水平的调制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的谷氨酸能传递和I组代谢型谷氨酸受体（mGluR）效应。多巴胺也在杏仁核的线索相关事件中起作用。拟议的实验将测试的假设，从慢性可卡因戒断2周后，神经传递和可塑性的持续变化是特定的杏仁核途径和代谢型谷氨酸和多巴胺能受体的调制。在这些实验中，杏仁核内通路中的突触传递使用尖电极、全细胞贴片和杏仁核切片中的细胞外记录来记录。总体目标是分析慢性可卡因戒断后线索相关可卡因记忆的膜测量，具体而言： 1.表征慢性可卡因戒断过程中神经元突触传递和可塑性对代表药物相关线索的刺激的改变，并确定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，并确定慢性可卡因戒断后的潜在信号机制。这些研究将确定慢性可卡因戒断后神经适应和药物相关线索的杏仁核内通信的突触机制，并可能导致新的和更合理的策略来阻止线索诱导的可卡因成瘾复发。

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.