Fast Changes in Glutamate in Response to Cocaine

可卡因引起的谷氨酸快速变化

• 批准号: 7493023
• 负责人: KEN TARO WAKABAYASHI
• 金额: $ 1.09万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7493023
• 关键词: Address; Amino Acids; Amygdaloid structure; Animal Model; Animals; Anterior; Area; Aspartate; Behavior; Behavioral; Brain; Brain region; Capillary Electrophoresis; Cells; Chemicals; Chromosome Pairing; Chronic; Cocaine; Cocaine Dependence; Collection; Coupled; Cues; Cysteine; Data; Detection; Development; Dopamine; Drug Addiction; Drug Delivery Systems; Drug Exposure; Drug usage; Event; Extracellular Space; Fellowship; Fluorescence; Gene Expression; Glutamates; Glycine; Goals; Human; In Vitro; Individual; Infusion procedures; Injection of therapeutic agent; Lasers; Lead; Methodology; Methods; Microdialysis; Modeling; Modification; Monitor; Motivation; Names; Neurobiology; Neuroglia; Neurons; Neurotransmitters; Nucleus Accumbens; Pharmaceutical Preparations; Prefrontal Cortex; Process; Public Health; Rate; Rattus; Relapse; Reporting; Research; Resolution; Rodent Model; Role; Route; Sampling; Serine; Signal Transduction; Source; Synapses; System; Taurine; Techniques; Technology; Thinking; Time; Ventral Tegmental Area; Work; absorption; addiction; antiporter; base; cingulate cortex; drug administration rate; drug relapse; experience; extracellular; gamma-Aminobutyric Acid; human study; in vivo; indexing; insight; interest; neural circuit; neurochemistry; neuromechanism; relating to nervous system; research study; response

Cocaine addiction is a persistent and significant public health problem with a strong neurobiological basis. Studies have identified key regions of the brain and neurotransmitter systems that change with chronic cocaine use. Altered glutamate signaling in the accumbens is suspected as one of the key factors in the transition from casual drug taking to chronic use. Glutamate signaling is involved in two rat models of addiction: psychomotor sensitization and reinstatement. Little is known of rapid glutamate signaling in these models. Methods of directly sampling extracellular glutamate in the brain with microdialysis has been limited by technology with poor time resolution. With capillary electrophoresis coupled with laser induced fluorescence, we are able to have subminute resolution for the first time with microdialysis. Changes in the fast modulation of extracellular glutamate may be the neurochemical mechanism by which the brain changes in response to cocaine. Thus, we hypothesize that cocaine experience will alter this rapid modulation of glutamate during sensitization and reinstatement. These experiments will provide insight into the contribution of these fast changes in glutamate to the neural mechanisms underlying cocaine addiction.

可卡因成瘾是一个具有强大神经生物学基础的持续和重大的公共卫生问题。 研究已经确定了大脑和神经递质系统的关键区域， 可卡因的使用谷氨酸信号的改变被怀疑是神经系统中的关键因素之一。 从偶尔吸毒到长期吸毒的转变。谷氨酸信号传导参与了两种大鼠模型， 成瘾：心理敏感化和恢复。在这些细胞中，对快速谷氨酸信号知之甚少。 模型利用微透析技术直接采集脑细胞外谷氨酸的方法有限 时间分辨率很差的技术。毛细管电泳-激光诱导 荧光，我们能够有亚分钟分辨率的第一次与微透析。变化 细胞外谷氨酸盐的快速调节可能是大脑变化的神经化学机制 对可卡因的反应。因此，我们假设可卡因的经验将改变这种快速调制， 谷氨酸在致敏和恢复过程中。这些实验将提供深入了解的贡献 谷氨酸的快速变化与可卡因成瘾的神经机制之间的联系。