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.
Zimatkin
S M
SM
Grodno State Medical University, Grodno, Belarus.
Liopo
A V
AV
Slychenkov
V S
VS
Deitrich
R A
RA
D000079:Acetaldehyde / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000378:metabolism* / Q000494:pharmacology*; D000431:Ethanol / Q000378:metabolism* / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D051381:Rats; D012890:Sleep / Q000187:drug effects / Q000235:genetics; D013997:Time Factors
D002492:Central Nervous System Depressants; D006993:Hypnotics and Sedatives; D000431:Ethanol; D002374:Catalase; D000079:Acetaldehyde