Fast Changes in Glutamate in Response to Cocaine

描述(申请人提供)：可卡因成瘾是一个持久和重大的公共卫生问题，具有很强的神经生物学基础。研究已经确定了大脑的关键区域和神经递质系统会随着长期使用可卡因而改变。伏隔核谷氨酸信号的改变被认为是从偶尔吸毒转变为慢性吸毒的关键因素之一。谷氨酸信号涉及两种成瘾大鼠模型：精神运动敏感化和恢复。人们对这些模型中的快速谷氨酸信号知之甚少。用微透析直接采集脑细胞外谷氨酸的方法受到时间分辨率较差的技术的限制。采用毛细管电泳联用激光诱导荧光技术，首次实现了微渗析的亚微米分辨率。细胞外谷氨酸快速调制的变化可能是大脑对可卡因反应发生变化的神经化学机制。因此，我们假设可卡因的经历将改变谷氨酸在敏化和恢复过程中的这种快速调节。这些实验将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.