Research described in this application will assess the mechanisms by which ascorbate modulates neostriatal neuronal activity. Possible interactions with dopamine or glutamate will be assessed in behaviorally distinct neuronal populations. The effects of ascorbate pretreatment on dopamine-mediated behavioral responses will be examined in parallel studies using simultaneous voltammetric procedures to obtain quantitative data on real-time neostriatal ascorbate release. Attention will center on the ability of ascorbate to alter open-field behavioral activity induced by dopamine agonists as well as performance on a lever-release conditioned avoidance response task known to depend on neostriatal dopamine transmission. A separate line of investigation will combine voltammetry with intracerebral infusions of glutamate or dopamine agonists to identify the processes underlying the ability of haloperidol, a neuroleptic and dopamine antagonist, to enhance neostriatal ascorbate release during long-term treatment.
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