A substantial amount of clinical evidence indicates that alcohol during pregnancy can produce both morphological and behavioral abnormalities in offspring. Animal studies have extended these clinical findings by documenting both morphological and behavioral effects of prenatal ethanol exposure under conditions of nutritional and environmental control impossible in the humans. In addition to confirming clinical findings, animal studies suggest that the effects of prenatal ethanol exposure extend to the fully mature offspring. Although the animal studies have documented both the morphological and behavioral abnormalities, the former have utilized mice whereas the latter have utilized rats. The studies described in this proposal will extend previous work on the behavioral effects of prenatal ethanol exposure by utilizing another species and by examining the basis for previously reported abnormalities of these offspring on several behavioral tasks. The studies will use a mouse strain which has been documented to show the classic teratogenic effects of ethanol; hence if behavioral effects are also present, a more complete model of prenatal ethanol effects in humans will be provided. To help establish a behavioral mechanism for some of the task performance differences between prenatally ethanol exposed and control rats, studies are proposed to examine the role of stimulus and response parameters in perseverative behavior and abnormal performance on conditioned avoidance tasks commonly reported for these offspring. Since memory deficits might also contribute to the abnormal performance on many of the tasks and is of tremendous concern for humans but, largely ignored in the animal literature, studies are proposed to examine the effects of prenatal ethanol on memory. Finally, since animal studies suggest that some of the effects of prenatal ethanol exposure are age-dependent, studies are proposed to examine the effects of prenatal ethanol on the ontogeny of activity and passive-avoidance behavior. The ultimate goal of our research in this area is to provide a comprehensive model of the Fetal Alcohol Syndrome in mice which will enable examination of issues of clinical relevance such as assessment of intervention strategies and assessment of the interaction of ethanol with nutritional deficiency or other drugs.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
1R01AA006611-01
Application #
3109826
Study Section
Alcohol Psychosocial Research Review Committee (ALCP)
Project Start
1985-05-01
Project End
1988-04-30
Budget Start
1985-05-01
Budget End
1986-04-30
Support Year
1
Fiscal Year
1985
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
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; 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
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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