THE EFFECTS OF ETHANOL ON RAT BRAIN. A. ACETALDEHYDE CONCENTRATION. B. FATTY ACID COMPOSITIONS. C. (SODIUM ION + POTASSIUM ION)-ATPASE ACTIVITY
Abstract
Recent theory suggests that adaptive alterations in neural membrane fatty acid composition occur during chronic consumption of alcohol. Fatty acid composition of brain membranes were determined in control and ethanol dependent rats. Regional analysis of synaptosomes showed that the cerebral cortex was the only area in which a statistically significant compositional change occurred. Chronic ethanol ingestion caused a 5-7% decrease in arachidonic acid in these membranes. After ethanol dependent rats were withdrawn from ethanol, arachidonic acid levels were still significantly reduced after three days, but not after ten. Alterations in diet affected the magnitude of the ethanol-induced arachidonic acid decrease, this reduction ranging from 2-10%. The other major polyunsaturated fatty acid, docosahexaenoic acid, increased in ethanol dependent animals with the size of the increase being positively correlated with the degree of the arachidonic acid decrease. Chronic administration of t-butyl alcohol caused a 5-11% increase in arachidonic acid and a 3-14% increase in docosahexaneoic acid. These small alcohol-induced alterations in fatty acid composition would not be expected to cause any gross changes in the physical properties of neural membranes. Plasma and liver phospholipid fatty acid compositions were also determined in these animals. Ethanol and t-butyl alcohol consumption produced different effects on composition. Ethanol caused a 6-20% decrease in arachidonic acid and a 30-40% increase in docosahexaenoic acid in liver; t-butyl alcohol caused a 12-21% increase in stearic acid. Other dietary dependent alterations in composition were found. The magnitude of the alcohol-induced fatty acid alterations was in most cases smaller than that caused by changes in diet alone. The effects of chronic administration of ethanol on synaptosomal (Na('+) + K('+))-ATPase activity and its inhibition by ethanol in vitro was also determined. At temperatures above 22(DEGREES)C, ethanol inhibited enzyme activity in a dose and temperature dependent manner. At temperatures below 22(DEGREES)C, activity was increased by the presence of 0.48 M ethanol in the assay media. No differences were found in the effects of ethanol on ATPase activity when enzyme from control and ethanol dependent rats were compared. Arrhenius plots revealed that no consistent differences existed between control and ethanol dependent rat ATPase. This suggests that chronic administration of ethanol did not cause any significant alterations in the micro-environment surrounding (Na('+) + K('+))-ATPase.(') Since acetaldehyde formed during ethanol oxidation has been suggested to mediate some of ethanol's effects on the central nervous system, acetaldehyde concentrations in the brains of rats metabolizing ethanol were determined. Ethanol was administered to rats and samples from blood and brain collected. Brain interstitial fluid samples were collected from the caudate nucleus and the thalamus-hypothalamus region using the push-pull perfusion technique. Blood ethanol levels typically ranged from 40 to 90 mM, while acetaldehyde levels ranged from 15 to 40 (mu)M in blood and 5 to 20 (mu)M in brain fluid. When disulfiram was given to the rats, blood acetaldehyde increased to 70-280 (mu)M and brain interstitial fluid acetaldehyde increased to between 25 and 120 (mu)M. No acetaldehyde could be detected in whole brain unless the animal had first been treated with disulfiram. These data demonstrate that acetaldehyde does enter the brain during ethanol intoxication. The acetaldehyde concentration in the interstitial fluid is higher than that in the brain cells, probably due to its rapid oxidation in cells by aldehyde dehydrogenase.
Degree
Ph.D.
Subject Area
Biology
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