Ascorbate, a water.soluble vitamin found in high concentrations in the mammalian forebrain, appears to modulate several different neural functions. This neuromodulatory role is especially evident in the neostriatum where physiological amounts of absorbate have been shown to alter neuronal activity and to interfere with the behavioral response to drugs that act in part via neostriatal mechanisms. To determine the neurochemical systems and processes underlying these actions of ascorbate a series of experiments will focus on a ppossible interactions between ascorbate and some well.known neurotransmitters. Single.unit recording techniques, including electrochemically.quantified iontophoresis, will be used to examine the effects of ascorbate on the neuronal response to iontophoretically.applied dopamine and glutamate and to glutamate released endogenously from cortico.neostriatal terminals. Intraneostriatal infusions in freely.moving rats will be used to examine the role of the neostriatum in the behavioral effects of ascorbate. Parellel experiments will examine the mechanisms that control extracellular levels of ascorbate, especially the dramatic rise produced by amphetamine. Carbon.fiber microvoltammetic and electrochemically.modified electrodes will be used to obtain unequivocal information on extracellular ascorbate levels in the neostriatum. Follow.up work will extend these investigations to other forebrain regions known to contain a high endogenous level of ascorbate. These lines of research will provide basic information about the mechanisms by which ascorbate regulates and controls some important neural and behavioral processes.