Relationship of Brain Ethanol Metabolism to the Hypnotic Effect of Ethanol. I: Studies in Outbred Animals

Background : This study was designed to investigate the relationship between the ethanol‐oxidizing capacity of the brain, accumulation of acetaldehyde, and ethanol‐induced hypnosis in animals in vivo. Methods: Randomly outbred albino rats were treated with ethanol, and the duration of ethanol‐induced loss of the righting response (sleep time) was measured. They were killed 2 weeks later (without further in vivo administration of ethanol), and brain homogenates were prepared to measure the accumulation of acetaldehyde from ethanol added in vitro. In a similar way, we determined the sleep time and, 5 days later, the rates of acetaldehyde accumulation in brains of heterogeneous mice. Results: Significant correlations between the duration of ethanol‐induced sleep and acetaldehyde accumulation in vitro were found. The Km value of the process of acetaldehyde accumulation was lower in long‐sleeping, as compared with short‐sleeping, rats. A similar result was also obtained in genetically heterogeneous mice. Animals with a longer duration of ethanol‐induced sleep had a higher level of the accumulation of ethanol‐derived acetaldehyde in brain homogenates, as compared with the short‐sleeping mice. Rats and mice with the intermediate duration of ethanol‐induced sleep had an intermediate value of acetaldehyde accumulation in brain homogenates. There was no correlation between brain catalase activity and ethanol‐induced loss of the righting response in either the rats or the mice. Conclusions: This study is a direct demonstration of the positive correlation between ethanol‐derived acetaldehyde accumulation in vitro in the brain and a central (behavioral) effect of alcohol in outbred rats and mice in vivo.