MODERATE ETHANOL CONSUMPTION BY THE PREGNANT GUINEA PIG INCREASES ETHANOL PREFERENCE IN OFFSPRING
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Ethanol teratogenicity involving the developing brain is the leading preventable cause of mental deficiency in the Western world. Chronic prenatal ethanol exposure (CPEE) may be a risk factor for ethanol abuse and altered responsiveness to nicotine in postnatal life. Previous studies in our laboratory have utilized maternal oral administration of a high-dose (4 g ethanol/kg maternal body weight/day) ethanol regimen that induces structural and functional deficits in the fetus and postnatal offspring. The objective of this thesis was to test the hypotheses that moderate CPEE produces in postnatal offspring: (i) structural and functional teratogenic effects; (ii) increased ethanol preference; (iii) altered responsiveness to acute nicotine; and (iv) increased nicotinic acetylcholine receptors (nAChR) in forebrain structures, namely the hippocampus and frontal cortex. Pregnant Dunkin-Hartley-strain guinea pigs were given 24-h access to aqueous ethanol solution (5%, v/v) sweetened with sucralose (1g/L) or aqueous sucralose solution (1g/L) throughout gestation. Spontaneous locomotor activity in an open field was measured in offspring on postnatal day (PD) 10. Beginning around PD 40, ethanol preference in the offspring was determined using a two-bottle-choice paradigm. Each animal was given 2-h daily access to aqueous ethanol solution (0 - 3%, v/v) and water over 33 days of testing. Subsequently, hippocampal and frontal cortical tissues were obtained for the measurement of nAChR population by radioligand binding. Moderate maternal consumption of the aqueous ethanol produced growth restriction in postnatal offspring of both sexes, and increased spontaneous locomotor activity in male offspring only. These postnatal outcomes are similar to the teratogenic effects produced by a high-dose, binge-type ethanol regimen. Compared with control, offspring from mothers that consumed ethanol throughout gestation exhibited greater preference for aqueous ethanol, and a decrease in the concentration of nAChRs in the frontal cortex, but not the hippocampus. These data demonstrate that, in the guinea pig, moderate maternal consumption of ethanol is a useful model for studying ethanol neurobehavioural teratogenicity; and chronic prenatal exposure to ethanol enhances ethanol preference in young adult offspring and altered expression of nAChRs in the frontal cortex.