Fast Changes in Glutamate in Response to Cocaine

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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.