Different dose levels of ethanol (2,3,4,5 g/kg) were administered to rat pups between postnatal days 4 and 10. Ethanol caused a dose-dependent decrease in brain weight (measured on postnatal day 12) and inhibition of carbachol-stimulated phosphoinositide metabolism (measured in cerebral cortex slices on postnatal day 7). The 2 g/kg dose, which gave blood alcohol levels of 128 mg/dl, was a no-effect-level for both endpoints. Ethanol administration did not alter the relative distribution of phosphoinositides in the cerebral cortex from 7 day-old rats. These results show a dose-dependent correlation between ethanol-induced microencephaly and inhibition of muscarinic receptor-stimulated phosphoinositide metabolism and add support to the hypothesis that this second messenger system may be involved in the developmental neurotoxicity of ethanol.
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