Extracellular ascorbate modulates cortically evoked glutamate dynamics in rat striatum

To determine if extracellular ascorbate, which may increase by several hundred micromolar in striatum during behavioral activation, directly alters glutamate transmission, we monitored striatal glutamate transients evoked by electrical stimulation of cerebral cortex in anesthetized rats tested with varying concentrations of ascorbate (0, 50, 200, and 500 μM) by reverse dialysis. Capillary electrophoresis coupled with laser-induced fluorescence detection was used to analyze dialysates collected at 3-s intervals. Ascorbate elevated striatal glutamate in a concentration-dependent fashion. Addition of 500 μM ascorbate not only more than doubled basal glutamate levels relative to the ascorbate-free condition, but significantly increased both the magnitude of the electrically evoked glutamate response as well as its subsequent return to baseline. In fact, the time required to return to within 10% of the pre-stimulation baseline increased by >100 s. Reverse dialysis of iso-ascorbate, in contrast, had no effect on stimulation-evoked glutamate release arguing against an antioxidant effect. It appears, therefore, that the level of extracellular ascorbate plays a critical role in regulating corticostriatal glutamate transmission.