Extracellular ascorbate modulates glutamate dynamics: role of behavioral activation

Background: A physiological increase in extracellular ascorbate (AA), an antioxidant vitamin found throughout the striatum, elevates extracellular glutamate (GLU). To determine the role of behavioral arousal in this interaction, microdialysis was used to measure striatal GLU efflux in rats tested in either a lights-off or lights- on condition while reverse dialysis either maintained the concentration of AA at 250 mu M or increased it to 1000 mu M to approximate endogenous changes. Results: When lights were off, both locomotion and GLU increased regardless of AA dose. In contrast, animals in the lights- on condition were behaviorally inactive, and infusion of 1000, but not 250, mu M AA significantly increased extracellular GLU. Interestingly, when ambient light returned to the lights- off group, 1000 mu M prolonged the GLU increase relative to the 250 mu M group. Conclusion: Our results not only support evidence that elevated striatal AA increases extracellular GLU but also indicate that this effect depends on behavioral state and the corresponding level of endogenous GLU release.