The long-range goal of this program of studies is to characterize alcohol-neuroendocrine and alcohol-neuroimmunologic interactions which impair learning and memory functions in alcoholics. To accomplish this objective, we propose to define more clearly the effects of alcohol administration on: 1) neuropeptide cells containing vasopressin (VP) or oxytocin (OT); catecholaminergic cells containing the key enzyme tyrosine hydroxylase (TH); and, their respective mRNA's, 2) VP, OT and dopamine (DA) secretion in vitro, and 3) blood-brain barrier mechanisms for transport of albumins and IgG's. The laboratory rat will be used as an experimental animal model for comparison of VP/OT, TH and their respective mRNA's found in similar regions of postmortem brains of human alcoholics and age-matched controls. The treatment group of rats will be administered either an alcohol or control liquid diet using the simultaneous pair-feeding system, and in the case of the withdrawal group, allowed a recovery period following treatment. Radioimmunoassay (RIA) will be used to quantify amounts of VP and OT, whereas immunoblotassay (IBA) will be used to quantify the mass of TH. Light microscopic immunocytochemistry (ICC) and in situ hybridization (ISH) techniques will be used to determine numbers of cells expressing VP/OT and TH relative to those containing their respective mRNA's in serial-sectioned brains. Computer morphometric and 3-dimensional graphic reconstruction techniques will be used to analyze more precisely the nuclear and subnuclear groups of neurons affected by alcohol. Since VP, OT, DA and an intact blood-brain barrier affect learning and memory function, the correlative analysis of results from these various methods should elucidate some of the biochemical and morphological alterations alcohol may have on neuroendocrine and catecholaminergic circuits.
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