Temporal correlation of changes in rat brain sialic acid and in inhibition of Na+-K+ ATPase with ethanol tolerance.

Administration of ethanol to rats by gavage, in daily doses increasing gradually from 3 to 6 g/kg, led to progressive development of tolerance to the hypothermic effect of test doses of ethanol (3 g/kg, i.p.), between days 4 and 21 of treatment. Tolerance was decreased by day 3 of withdrawal, and had disappeared by day 7. Basal levels of brain microsomal Na+-K+ ATPase activity increased progressively during tolerance development, and returned to normal by 4 days after ethanol withdrawal. Conversely, inhibition of the ATPase by ethanol alone (0.22-0.66 M), or by 1 microM norepinephrine (NE) combined with much lower concentrations of ethanol (0.0125-0.1 M), decreased progressively during tolerance development, and returned to normal after withdrawal. The best temporal correlation with the degree of tolerance was shown by the magnitude of NE sensitization of the enzyme to ethanol inhibition. The chronic sucrose control treatment resulted in an unexplained increase in the NE sensitization. Since synaptosomal membrane concentration of sialic acid showed a similar time course during ethanol treatment, it is possible that changes in membrane sialic acid contribute to the alteration in NE sensitization by altering NE receptor properties.