In an attempt to elucidate possible causes of the neural abnormalities associated with the Fetal Alcohol Syndrome/Effects this laboratory has examined the influence of chronic maternal ethanol consumption, prior to parturition, on CNS development in rat offspring. Recent observations are potentially quite significant. This laboratory has found that in utero ethanol exposure results in a large reduction of serotonin (5-HT) and the acid metabolite, 5-hydroxyindole 3-acetic acid (5-HIAA), in the cortex (5-HT reduced by 50%), cerebellum and brain stem. The 5-HT and 5-HIAA deficiency persists until at least 5 weeks after the animals' last exposure to ethanol. Cortical dopamine (DA) and the acid metabolite, homovanillic acid (HVA), were also substantially reduced (to 22% normal DA) in the 5-week-old offspring of ethanol-fed rats. The present studies will determine the cortical region(s) in which the deficiencies of 5-HT, 5-HIAA, DA and HVA are localized. The present studies will also determine whether the deficiencies of the neuroamines are permanent. Neuroamines and acid metabolites will be separated and quantitated using high performance liquid chromatography and electrochemical detection. In addition, the proposed studies will determine wehther the observed deficiencies of 5-HT and DA are indicative of a delay in the development of the serotonergic and dopaminergic systems.
The aim will be accomplished by: 1) examining the development of presynaptic uptake systems for 5-HT and DA, as an assessment of presynaptic terminal development; and 2) examining the development of high affinity receptors for 5-HT and DA. Serotonin and dopamine uptake will be studied using radioligands ([3H]-serotonin and [3H]-dopamine) and inhibitors of serotonin and dopamine uptake (fluoxetine and nomifensine). High affinity receptors will be determined using specific ligands and concentrations of ligands which selectively label the high affinity binding sites for serotonin (S1 and S2) and dopamine (D1 and D2). The results of these experiments will provide important information about the cortical localization and duration of deficiencies of dopamine and serotonin, that result from in utero ethanol exposure in the rat. The results will also provide important information about the influence of chronic maternal ethanol consumption on the development of presynaptic uptake systems and high affinity binding sites for serotonin and dopamine in offspring.
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