A substantial amount of clinical evidence indicates that alcohol during pregnancy can produce morphological and behavioral abnormalities in offspring. Animal studies have confirmed these observations under nutritionally and environmentally controlled conditions unattainable in the humans and have established ethanol exposure as the most likely causative agent. In addition, the animal studies indicate that some of the behavioral deficits can extend to the fully mature adult. Research from our project established that C57BL/6 mice exposed to ethanol prenatally had reduced body weight and several behavioral deficits postnatally including impaired short term memory and an inappropriate response to positive reinforcement. Since this strain is also susceptible to the teratogenic effects of ethanol, it appears to provide a comprehensive rodent model for studying the effects of prenatal alcohol exposure. Included among the postnatal effects of prenatal alcohol exposure in our studies were three results distinguishable from previous reports and are the basis for the proposed research. First, prenatal ethanol exposed mice had weight reductions which were not manifest until around the time of weaning and lasted into adulthood; second, their behavior was less influenced than controls by positive reinforcement or by ethanol; and third, they were less able than controls to discriminate the systemic presence of ethanol. Both effects persisted into adulthood and are likely permanent. The studies described in this proposal are to characterize these effects and investigate potential mediating mechanisms. Currently there is no evidence for these findings in humans prenatally exposed to ethanol. Due to the time lapse between prenatal exposure and the manifestation of these effects it is doubtful that such investigations would be undertaken unless prompted by the results of animal experiments. It is hoped that the proposed studies will help establish the conditions under which these phenomena occur and a possible mechanism for each thus provide the stimulus for similar investigations in humans.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
2R01AA006611-04A1
Application #
3109828
Study Section
Alcohol Biomedical Research Review Committee (ALCB)
Project Start
1985-05-01
Project End
1992-12-31
Budget Start
1989-01-01
Budget End
1989-12-31
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Medical University of South Carolina
Department
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
Groseclose, C H; Middaugh, L D (1997) The discrimination and durability of an ethanol cue in young and mid-aged female mice. Alcohol 14:191-7
Boggan, W O; Xu, W; Shepherd, C L et al. (1996) Effects of prenatal ethanol exposure on dopamine systems in C57BL/6J mice. Neurotoxicol Teratol 18:41-8
Middaugh, L D; Boggan, W O (1995) Perinatal maternal ethanol effects on pregnant mice and on offspring viability and growth: influences of exposure time and weaning diet. Alcohol Clin Exp Res 19:1351-8
Middaugh, L D; Boggan, W O; Shepherd, C L (1994) Prenatal ethanol effects and dopamine systems of adult C57 male mice. Neurotoxicol Teratol 16:207-12
Middaugh, L D; Gentry, G D (1992) Prenatal ethanol effects on reward efficacy for adult mice are gestation stage specific. Neurotoxicol Teratol 14:365-70
Middaugh, L D; Bao, K; Shepherd, C L (1992) Comparative effects of ethanol on motor activity and operant behavior. Pharmacol Biochem Behav 43:625-9
Middaugh, L D; Frackelton, W F; Boggan, W O et al. (1992) Gender differences in the effects of ethanol on C57BL/6 mice. Alcohol 9:257-60
Hale, R L; Randall, C L; Becker, H C et al. (1992) The effect of prenatal ethanol exposure on scentmarking in the C57BL/6J and C3H/He mouse strains. Alcohol 9:287-92
Bao, K; Middaugh, L D; Becker, H C et al. (1992) Effects of Ro 15-4513 and ethanol on operant behavior of male and female C57BL/6 mice. Alcohol 9:193-8
Middaugh, L D; Boggan, W O (1991) Postnatal growth deficits in prenatal ethanol-exposed mice: characteristics and critical periods. Alcohol Clin Exp Res 15:919-26

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