Fast Changes in Glutamate in Response to Cocaine

可卡因成瘾是一个持久而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随着慢性疾病的变化 可卡因的使用。伏隔核谷氨酸信号的改变被怀疑是导致 从偶尔吸毒过渡到长期吸毒。谷氨酸信号转导参与了两种大鼠模型 成瘾：精神运动敏感化和恢复。对这些细胞中的快速谷氨酸信号知之甚少 模特们。用微透析法直接采集脑细胞外谷氨酸的方法受到限制 时间分辨率很差的技术。毛细管电泳联用激光诱导 荧光，我们第一次能够通过微渗析获得亚分钟分辨率。的变化 细胞外谷氨酸的快速调制可能是大脑改变的神经化学机制 对可卡因的反应。因此，我们假设可卡因的经历将改变这种快速调节 敏化和恢复过程中的谷氨酸。这些实验将提供对贡献的洞察 这些谷氨酸的快速变化与可卡因成瘾的神经机制有关。

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.