Blood alcohol concentration and severity of microencephaly in neonatal rats depend on the pattern of alcohol administration.
A rat model of third trimester fetal alcohol exposure was used to examine how the pattern of administration of a daily alcohol dose influences the pattern of blood alcohol concentrations (BACs) and the severity of brain growth restriction. Four groups of rats were artificially reared from postnatal days 4 to 10. Three of the groups received an equivalent daily dose of alcohol (6.6 g/kg/day) but in different daily patterns. To one group, the dose was administered continuously in a 2.5% (v/v) solution; in two other groups, the dose was condensed into either 7.5% or 15.0% (v/v) solutions. A fourth group (gastrostomy controls) received a formula containing maltose-dextrin, which was isocaloric to the 2.5% alcohol solution. BACs were determined twice daily at times designed to estimate the daily peak and minimum BACs. The rats were killed on postnatal day 10 and total brain weights, cerebellar weights and brainstem weights were measured. In each of the three groups given alcohol, the maximum BAC occurred on the afternoon of postnatal day 6. Thereafter, daily peak BAC declined progressively. The more concentrated the pattern of alcohol administration, the higher was the maximum BAC achieved and the more severe was the interference with brain growth. While the group receiving the alcohol dose in small continuous fractions (2.5%) did not exhibit any significant microencephaly, relative to gastrostomy controls, the groups receiving the dose in more concentrated forms (7.5% and 15.0%) exhibited significant brain growth restriction (reduced 19% and 31%, respectively, relative to controls).(ABSTRACT TRUNCATED AT 250 WORDS)
Bonthius
D J
DJ
Department of Anatomy, College of Medicine, University of Iowa, Iowa City 52242.
Goodlett
C R
CR
West
J R
JR
D000428:Alcohol Drinking / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000493:pharmacokinetics*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000097:blood*; D005865:Gestational Age; D008297:Male; D008431:Maternal-Fetal Exchange; D008831:Microcephaly / Q000097:blood*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains
D000431:Ethanol