Altered sensitivity to ethanol following prenatal exposure to barbiturate

Female mice (genetically heterogeneous stock) were fed milled mouse food containing 3 g/kg phenobarbital (PhB) and water as their only nutritional source from gestation days 9-18. Control dams received milled food and water. Blood PhB levels of treated females and fetuses were 40-200 μg/ml. At the age of 50 days, male offspring were injected with 3.5 g/kg ethanol. Sleep time was monitored and in randomly selected individuals, brain ethanol levels were determined upon awakening. To assess the rate of metabolism in the treated and control offspring, blood ethanol levels were determined in other randomly selected individuals at 60 and 120 min post-injection. Offspring who received PhB prenatally were resistant to the hypnotic effects of ethanol as evidenced by their 33% shorter sleep time compared to controls (P<0.001). The brain ethanol levels upon awakening were higher than control in the offspring born to the barbiturate-treated mothers (P<0.001), indicating that the resistance to ethanol was due to factors residing within the central nervous system.