The dorsolateral striatum is involved in mediating habit learning. This habit learning is involved in ritualizatlon of behaviors related to compulsive drug use. It has been reported that acute cocaine administration results in increased expression of the immediate early gene, c-Fos. Furthermore, this cocaine-induced expression can be blocked by prior administration of glutamate receptor antagonists. However, the long-term effects on glutamate in the dorsolateral striatum after acute cocaine administration is not known. The primary goal of this proposal is to investigate the neurochemical and neuroanatomicai changes within the dorsolateral striatum that occur as a result of acute cocaine administration. In vivo microdialysis will be used to determine the striatal changes in extracellular glutamate after an acute cocaine injection. Immunogold electron microscopy will be used to correlate changes in extracellular glutamate with alterations in the density of presynaptic nerve terminal glutamate immunolabeling. To investigate whether cocaine is having an indirect effect on striatal glutamate via the thalamocorticostdatal pathway, the motor thalamic nucleus will be lesioned prior to acute cocaine exposure. Knowledge of the short and long term effects of a single cocaine exposure could promote a better understanding of cocaine use by humans.