DOPAMINE FUNCTION IN MIDBRAIN

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Animals and humans exposed to ethanol in utero exhibit altered motor activity and increased arousal. Based on an extensive clinical and preclinical literature which indicates that these functions are influenced by mesencephalic dopamine (DA) systems, we hypothesized that these neuronal systems might be altered by prenatal ethanol exposure. Preliminary observations detailed within this proposal indicate that this hypothesis was correct. This proposal details a complete examination of the influence of in utero ethanol exposure on dopamine neuronal systems. It outlines a series of interrelated studies which will examine changes in both presynaptic dopamine neurons and postsynaptic dopamine-sensitive cells. The analyses will include the detailed investigation of the number and morphology of dopamine neurons, evaluation of dopamine cell electrophysiology (firing rate and pattern), examination of the changes in various dopamine receptors (dopamine autoreceptors, D2 and D1 receptors), examination of altered G-protein mRNA expression, analysis of substance P and met-enkephalin mRNA expression, and examination of the dopamine transporter. Combined electrophysiological, immunohistochemical, biochemical and pharmacological methods will be employed. It is hoped that the findings obtained will provide new information regarding the influence of ethanol on the expression of normal adult characteristics of mesencephalic dopamine neuronal systems.