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 ac cumulation in vitro were found. The K-m 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.