Ascorbate Modulates Glutamate-induced Excitations of Striatal Neurons

To assess the role of ascorbate (AA), an antioxidant vitamin, in modulating striatal activity, single-unit recording was combined with iontophoresis in awake, unrestrained rats. Brief applications of AA (20 s, 5-80 nA) elicited few changes in either basal activity or activity evoked by continuous application of glutamate (GLU), but relatively high AA ejection currents (>40 nA) often inhibited fast-firing units. Comparable results were obtained with the antioxidant isomer, iso-AA, suggesting the AA-induced inhibition represents a high-dose, antioxidant effect. When applied for prolonged periods (2-4 min) at doses that failed to alter basal activity, AA either enhanced or attenuated the excitatory response to test pulses of GLU. The AA-induced enhancement occurred more frequently (16 vs. 6 applications) and was characterized by a more rapid (shorter onset and peak latencies) and more pronounced (greater peak magnitude) excitation to GLU without an evident change in offset latency. In most cases, further increases in AA ejection current attenuated the GLU response. Iso-AA, in contrast, had only inhibitory effects, which occurred at moderate- to high-dose applications. Collectively, these results suggest that AA, apart from its antioxidant effects, modulates phasic changes in striatal excitability induced by GLU. Because extracellular levels of striatal AA fluctuate in relation to behavioral activation, this neuromodulatory action of AA may contribute to behaviorally relevant changes in sensorimotor responsivity.