ADMINISTRATION OF ETHANOL DURING BRAIN GROWTH SPURT CAUSES DOSE-DEPENDENT MICROENCEPHALY AND INHIBITION OF MUSCARINIC RECEPTOR-STIMULATED PHOSPHOINOSITIDE METABOLISM IN THE RAT

Different dose levels of ethanol (2,3,4,5 g/kg) were administered to r at pups between postnatal days 4 and 10. Ethanol caused a dose - depen dent decrease in brain weight (measured on postnatal day 12) and inhib ition 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 distribu tion 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 - stimula ted phosphoinositide metabolism and add support the hypothesis that th is second messenger system may be involved in the developmental neurot oxicity of ethanol.