EFFECT OF CHRONIC MATERNAL ETHANOL ADMINISTRATION ON NITRIC-OXIDE SYNTHASE ACTIVITY IN THE HIPPOCAMPUS OF THE MATURE FETAL GUINEA-PIG

Nitric oxide is a novel messenger that is involved in neuronal cell-ce ll communication and seems to play a neurotrophic role in normal brain development Chronic prenatal ethanol exposure can produce central ner vous system (CNS) teratogenesis, in which one of the target sites is t he hippocampus. The main objective of our study was to test the follow ing hypothesis: chronic maternal administration of an ethanol dosage r egimen that produces CNS teratogenesis decreases nitric oxide synthase (NOS) activity in the fetal hippocampus. The ontogeny of NOS activity in the hippocampus of the developing guinea pig was further elucidate d at two prenatal and two postnatal ages. The effects of chronic mater nal oral administration of 4 g of ethanol/kg maternal body weight/day, isocaloric sucrose and pair feeding, or water [given as two equally d ivided doses 2 hr apart from gestational day (GD) 2 to GD dl] on body, brain, and hippocampal weights and hippocampal NOS activity were dete rmined in the mature fetal guinea pig at GD 62 (term, about GD 68). NO S activity in the 25,000 x g supernatant fraction of hippocampal homog enate was measured using an optimized radiometric assay, based on the oxidation of L-[C-14]arginine to L-[C-14]citrulline. For the chronic e thanol regimen, the maternal blood ethanol concentration at 1 hr after the second divided dose on GD 57 was 167 +/- 45 mg/dl. Chronic matern al administration of ethanol decreased fetal body, brain, and hippocam pal weights, compared with the isocaloric-sucrose/pair-fed and water t reatment groups. The rate of L-[C-14]citrulline formation and NOS acti vity in the fetal hippocampus were decreased in the ethanol treatment group, compared with the isocaloric-sucrose/ pair-fed and water treatm ent groups. There was no difference in the rate of L-[C-14]citrulline formation, NOS activity, and fetal hippocampal and body weights betwee n the isocaloric-sucrose/pair-fed and water treatment groups; however, fetal brain weight was decreased in the isocaloric-sucrose group, com pared with the water group. Data of this study support the research hy pothesis by demonstrating that chronic maternal administration of etha nol decreases fetal hippocampal NOS activity that is correlated with r estricted growth of this brain region.