Effects of chronic prenatal ethanol exposure on locomotor activity, and hippocampal weight, neurons, and nitric oxide synthase activity of the young postnatal guinea pig

Decreased nitric oxide synthase (NOS)-catalyzed formation of NO from L-argi nine may be involved in ethanol teratogenesis involving the hippocampus. Th is hypothesis was tested by determining the effects of chronic prenatal eth anol exposure on locomotor activity and on hippocampal weight, number of CA 1 and CA3 pyramidal cells and dentate gyrus granule cells, and NOS activity of the postnatal guinea pig. Timed, pregnant guinea pigs received one of t he following chronic oral regimens throughout gestation: 4 g ethanol/kg mat ernal body weight/day, isocaloric-sucrose/pair-feeding, or water. At postna tal day (PD) 10, spontaneous locomotor activity was measured. At PD 12, his tological analysis was performed on the hippocampal formation, in which hip pocampal CA1 and CA3 pyramidal cells and dentate gyrus granule cells were c ounted; body, brain, and hippocampal weights were measured; and hippocampal NOS enzymatic activity was determined using a radiometric assay. Chronic p renatal ethanol exposure produced hyperactivity, decreased the brain and hi ppocampal weights with no change in body weight, decreased the number of hi ppocampal CA1 pyramidal cells by 25-30%, and had no effect on hippocampal N OS activity compared with the two control groups. These data, together with our previous findings in the fetal guinea pig. demonstrate that chronic pr enatal ethanol exposure decreases hippocampal NOS activity in near-term fet al life that temporally precedes the selective loss of hippocampal CA1 pyra midal cells in postnatal life. (C) 2000 Elsevier Science Inc. All rights re served.