Amygdala Neurons and Cocaine

描述（由申请人提供）：杏仁核是大脑奖赏回路的一部分，在动物的可卡因寻求和戒断以及人类的渴望和复发中起作用。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中是必不可少的。然而，慢性可卡因对杏仁核神经元的膜效应尚不清楚，药物相关关联的潜在机制才刚刚开始被理解。本研究的长期目标是通过描述慢性可卡因戒断过程中突触水平杏仁核神经传递的调节和改变来分析可卡因线索相关信息的机制。慢性可卡因增强杏仁核神经元中谷氨酸能传递和I组代谢谷氨酸受体（mGluR）的作用。多巴胺还在杏仁核的线索相关事件中发挥作用。该实验将验证慢性可卡因戒断2周后神经传递和可塑性的持续改变是杏仁核通路所特有的，并由代谢性谷氨酸和多巴胺能受体调节。实验采用尖电极、全细胞贴片和杏仁核切片记录杏仁核内通路的突触传递。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，具体如下：

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.