Ethanol-induced changes in cation-stimulated adenosine triphosphatase activity and lipid-proteolipid labeling of brain microsomes.
The experiments described are based on the hypothesis that prolongation of the depressant action of ethanol leads to compensatory changes in neuronal membrane structures involved in impulse conduction and transmission, and that these become manifest as increased tolerance and withdrawal hyperexcitability. Behavioral tolerance was tested by means of the tilted plane test in rats consuming 9-10 g ethanol/kg/day in a liquid diet fed ad lib., or given 5 g/kg every other day by stomach tube, or doses rising from 6 to 9 g/kg/day maintaining continuous intoxication. All treatments were continued for about three or four weeks before testing. Rats consuming ethanol at a self-regulated rate did not develop tolerance, evidently because sufficient alcohol levels were not built up. Prolonged intoxication induced a high degree of tolerance and withdrawal symptoms, whereas intoxication every other day induced an intermediate degree of tolerance. When no definite abstinence symptoms were associated with the behavioral tolerance, cation stimulated ATPase activity of the brain microsomal fraction was not changed. With increasing withdrawal excitability, there was a relative increase in Na+, K+-stimulated ATPase and an decrease in Mg2+-stimulated ATPase whereas total activity of the enzyme system was not altered. 14C-serine was used as a precursor in order to detect changes in the metabolism of membrane components. So far, only acute experiments have been carried out in vivo. Heavy intoxication (6 g ethanol/kg by stomach tube) inhibited labeling of brain microsomal lipids and proteolipids. In "hangover", proteolipid labeling had returned to the control level whereas lipid labeling was still depressed. Cerebral cortex slices from rats in a withdrawal state after prolonged intoxication, and from control rats, were incubated in vitro with 14C-serine. Unstimulated tissue showed no effect of the prior treatment. When electrical stimulation was applied, much more activity was recovered in microsomal lipids of slices from withdrawal animals than from controls.
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000435:Alcoholic Intoxication / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D004789:Enzyme Activation / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D012964:Sodium / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000378:metabolism
D008074:Lipoproteins; D009419:Nerve Tissue Proteins; D000431:Ethanol; D012964:Sodium; D000251:Adenosine Triphosphatases; D008274:Magnesium; D011188:Potassium