Dysfunction of neuroendocrine and neurotransmitter activity has been linked to many of the psychological, social and pathophysiological consequences of alcoholism. The long term goal of this project is to determine the effects of alcohol on particular peptide- and catecholamine-containing neuronal systems using the laboratory rat as an experimental animal model for comparison with the same neurosubstances and regions of postmortem brains from human alcoholics. Neuroendocrine cells containing vasopressin (VP), oxytocin (OT), and beta-endorphin (B-E) will be quantified using radioimmunoassay (RIA), while immunonblotassay (IBA) will be used to measure enzymatic activity of tyrosine hydroxylase (TH). Light microscopic (LM-) and electron microscopic immunocytochemistry (EM-ICC) will be utilized to determine numbers of chemically-identified neuronal perikarya and their ultrastructural characteristics in animals administered alcohol vs. controls. The treatment group of rats will be administered either an alcohol or liquid control diet using the simultaneous pair- feeding system, and in the case of the withdrawal group, allowed a recovery period following treatment. The experimental paradigm used for the animal studies will determine the effects of alcohol both on the quantity of neurosubstances in micropunch samples of specific brain regions, and numbers of chemically- identified cell bodies. Similarly, RIA and IBA assays will be done in one-half, while numbers of cell bodies stained with LM-ICC will be counted in the other half of human brains of alcoholics vs. age-matched controls. Since VP, OT, B-E and catecholamines have been shown to play a role in learning and memory, then correlative analysis of results from these studies should elucidate the biochemical and morphological alterations alcohol may have on neuroendocrine and catecholaminergic circuits of the animal and human brain.
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