Use of inhalation to study the effect of ethanol and ethanol dependence on neonatal mouse development without maternal separation: a preliminary study.
This study explored the use of ethanol inhalation as a model to study the effects of ethanol and ethanol dependence on neonatal brain development in mice without maternal separation. In these experiments two day old Swiss Webster mice with their mothers were put in an inhalation chamber and continuously exposed to ethanol vapors for 12 days. The results indicate that: (a) the neonates developed substantial blood ethanol levels (160 to 290 mg/dl); (b) the mothers had minimal blood ethanol concentrations (BECs < 10mg/dl); (c) no mortality was observed during ethanol exposure; (d) physical dependence to ethanol was produced in the neonates, as evidenced by typical withdrawal symptoms.; (e) exposure to ethanol vapors did not affect the weight gain of the neonates indicating that nutrition and suckling ability was not significantly altered; the body weight of the mothers were also not affected; (f) 12 days of neonatal ethanol exposure significantly reduced whole brain and cerebellar weights on postnatal day 45 as compared to the controls; (g) neonatal ethanol exposure resulted in behavioral changes on postnatal day 40 to 41. Twelve days of ethanol exposure significantly impaired habituation, but did not alter spontaneous locomotion and (h) ethanol sensitivity on postnatal day 45 measured by Loss of Righting Reflex (LORR) was not affected. Although further studies are necessary, the results demonstrate that exposure to ethanol vapors can cause high BECs in the neonates without causing meaningful BECs in the mothers. Collectively, the results indicate that the ethanol inhalation technique can be used to investigate the effects of ethanol and ethanol dependence on neonatal development in mice during the rodent equivalent of the human third trimester.
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Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los Angeles 90033, U.S.A.
Alkana
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D000280:Administration, Inhalation; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D000831:Animals, Newborn / Q000097:blood / Q000254:growth & development*; D001835:Body Weight; D001921:Brain / Q000254:growth & development; D000431:Ethanol / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D006185:Habituation, Psychophysiologic; D007700:Kinetics; D051379:Mice; D009043:Motor Activity; D009929:Organ Size
D000431:Ethanol