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-arginine may be involved in ethanol teratogenesis involving the hippocampus. This hypothesis was tested by determining the effects of chronic prenatal ethanol exposure on locomotor activity and on hippocampal weight, number of CA1 and CA3 pyramidal cells and dentate gyrus granule cells, and NOS activity of the postnatal guinea pig. Timed, pregnant guinea pigs received one of the following chronic oral regimens throughout gestation: 4 g ethanol/kg maternal body weight/day, isocaloric-sucrose/pair-feeding, or water. At postnatal day (PD) 10, spontaneous locomotor activity was measured. At PD 12, histological analysis was performed on the hippocampal formation, in which hippocampal CA1 and CA3 pyramidal cells and dentate gyrus granule cells were counted; body, brain, and hippocampal weights were measured; and hippocampal NOS enzymatic activity was determined using a radiometric assay. Chronic prenatal ethanol exposure produced hyperactivity, decreased the brain and hippocampal weights with no change in body weight, decreased the number of hippocampal CA1 pyramidal cells by 25-30%, and had no effect on hippocampal NOS activity compared with the two control groups. These data, together with our previous findings in the fetal guinea pig, demonstrate that chronic prenatal ethanol exposure decreases hippocampal NOS activity in near-term fetal life that temporally precedes the selective loss of hippocampal CA1 pyramidal cells in postnatal life.
Gibson
M A
MA
Department of Pharmacology and Toxicology, Faculty of Health Sciences, Queen's University, Kingston, Ontario, Canada.
Butters
N S
NS
Reynolds
J N
JN
Brien
J F
JF
D000022:Abortion, Spontaneous; D000428:Alcohol Drinking; D000437:Alcoholism; D000818:Animals; D001724:Birth Weight; D018891:Dentate Gyrus / Q000033:anatomy & histology / Q000166:cytology; D005260:Female; D006168:Guinea Pigs; D006624:Hippocampus / Q000033:anatomy & histology* / Q000166:cytology / Q000201:enzymology; D008098:Litter Size; D008297:Male; D009043:Motor Activity; D009474:Neurons / Q000166:cytology / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D009929:Organ Size; D011247:Pregnancy; D011248:Pregnancy Complications; D011256:Pregnancy Outcome; D011297:Prenatal Exposure Delayed Effects; D017966:Pyramidal Cells / Q000166:cytology
D019001:Nitric Oxide Synthase