Fast Changes in Glutamate in Response to Cocaine

描述（由申请人提供）：可卡因成瘾是一种持续存在的重大公共卫生问题，具有很强的神经生物学基础。研究已经确定了大脑和神经递质系统的关键区域随着长期使用可卡因而发生变化。伏隔核谷氨酸信号的改变被怀疑是从偶然用药到长期用药转变的关键因素之一。谷氨酸信号参与了两种大鼠成瘾模型：精神运动致敏和恢复。在这些模型中，对谷氨酸快速信号传导知之甚少。微透析直接采集脑细胞外谷氨酸的方法一直受到时间分辨率差的技术的限制。毛细管电泳与激光诱导荧光相结合，首次实现了微透析的亚分钟分辨率。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，我们假设在致敏和恢复过程中，可卡因会改变谷氨酸的快速调节。这些实验将有助于深入了解谷氨酸快速变化对可卡因成瘾的神经机制的影响。

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.