There is evidence to suggest that the release of dopamine within the basal ganglia exhibits a circadian pattern and suggests a similar pattern in basal ganglia function. Immunocytochemical approaches will be used to study the distribution of dopamine and EAA receptors in the rat substantia nigra. The effects of circadian rhythms on these receptor distributions will be determined in melatonin-treated animals, as well as in others entrained to various lighting conditions. Subsequently, electrophysiological determinations of DA function, relative to motor mechanisms in the basal ganglia, will be evaluated. In addition, the humoral effects of melatonin on DA and EAA modulatory mechanisms in the substantia nigra will be studied in brain slices using conventional current-clamp as well as whole cell patch clamp techniques. We will also identify the functional role of each receptor subtype utilizing electrophysiological and pharmacological approaches (Aim II). Attempts will be made to correlate functional parameters with light/dark cycles and melatonin levels. Our findings will (i) contribute to the further understanding of glutamate and DA functions in the brain (ii) elucidate the identity and possible contribution of select DA and glutamate receptors in mechanisms of normal SNc function and (iii) delineate their role in circadian or melatonin control of CNS DA neuronal function.
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