APPLICANT'S DESCRIPTION: Recent efforts in this laboratory have produced innovative technologies of neurochemical monitoring in the extracellular space of the mammalian brain. Specifically, new strategies of the in vivo monitoring of dopamine, glutamate, choline, glucose, ascorbate, and oxygen have been devised. Past research with these devices has been conducted in anesthetized rats and in brain slices. The present application describes the adaptation of the new techniques to the detection of dopamine and glutamate in the extracellular space of the striatum in awake animals. Drugs that inhibit dopamine uptake from the extracellular space are believed to cause an increase in extracellular dopamine levels, and this increase is regarded as an important component of the mechanism of action of cocaine. Nevertheless, prior electrophysiological data suggest that uptake inhibitors shut down dopamine release, which suggests that a decrease in extracellular dopamine levels is to be expected. We will test the hypothesis that cocaine administration leads to a decrease in extracellular dopamine levels using a new strategy for the quantification of in vivo neurochemical results. A decrease in glutamatergic activity of the cortex is heavily implicated in schizophrenia, which creates a need to monitor glutamate in the extracellular space of brain structures that receive cortical projections. We will test the hypothesis that the neuronally derived component of extracellular glutamate levels in the striatum is under the regulation of the medial prefrontal cortex.