Amygdala Neurons and Cocaine

描述(申请人提供)：杏仁核，大脑奖励回路的一部分，在动物的可卡因寻找和戒断以及人类的渴望和复发中发挥作用。可卡因的激励动机与可卡因线索有关，而杏仁核在形成与药物相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膜的影响尚不清楚，与药物相关的联系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上的调制和修饰来分析与可卡因线索相关的信息的机制。慢性可卡因增强杏仁核神经元的谷氨酸能传递和I组代谢性谷氨酸受体(MGluR)作用。多巴胺也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一假设，即在慢性可卡因戒断2周后，神经传递和可塑性的持续变化是杏仁核通路特有的，并受到代谢性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片的细胞外记录，记录了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线索相关可卡因记忆的膜测量，具体地说： 1.表征慢性可卡因戒断过程中谷氨酸能突触传递和可塑性的变化，确定其潜在的信号机制；2.分析代谢性谷氨酸和多巴胺受体在调节突触传递和可塑性中的作用，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杏仁核内药物相关线索交流的突触机制，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.