Fast Changes in Glutamate in Response to Cocaine

描述（由申请人提供）：可卡因成瘾是一种具有强大神经生物学基础的持续性和重大公共卫生问题。研究已经确定了大脑和神经递质系统的关键区域，这些区域会随着长期使用可卡因而发生变化。改变的谷氨酸信号传导的药物被怀疑是一个关键因素的过渡，从偶然的药物服用到长期使用。谷氨酸信号参与了两种成瘾大鼠模型：精神敏化和复吸。在这些模型中，对快速谷氨酸信号传导知之甚少。利用微透析技术直接采集脑细胞外谷氨酸的方法受到时间分辨率差的技术限制。与毛细管电泳耦合激光诱导荧光，我们能够有亚分钟分辨率的第一次与微透析。细胞外谷氨酸快速调节的变化可能是大脑对可卡因反应的神经化学机制。因此，我们假设，可卡因的经验将改变这种快速调制的谷氨酸在致敏和恢复。这些实验将提供深入了解谷氨酸的这些快速变化对可卡因成瘾的神经机制的贡献。

DESCRIPTION (provided by applicant): 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.