Date of Award

1-1-1981

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Physiology and Pharmacology

Abstract

The role of extra- and intracellular acid-base status and divalent cations in the onset and severity of withdrawal from chronic ethanol intoxication was investigated in mice and rats. Body temperatures in both species were significantly decreased throughout withdrawal. While temperature corrected bicarbonate and extracellular pH, and brain Zn('++) concentrations were significantly increased in alcohol-exposed mice, all other parameters monitored in mice and rats indicate the lack of alkalosis or changes in Mg('++) or Ca('++) concentrations during withdrawal.The severity of withdrawal following chronic intoxication was not affected by either 5% or 15% CO(,2) therapy during the withdrawal period. Fifteen percent CO(,2) did however significantly elevate pCO(,2) in alcohol-exposed/CO(,2) and control/CO(,2) animals while significantly decreasing pHi in alcohol-exposed/CO(,2) animals. Brain cation concentrations following CO(,2) therapy remain unchanged. These data indicate that the onset and expression of withdrawal symptoms are not dependent upon the presence of respiratory alkalosis or alterations in whole brain cation concentrations.Data from metabolic profiles in mice during pretreatment, intoxication, and withdrawal periods indicate a significantly decreased urine volume in alcohol-exposed animals during intoxication and withdrawal which correlates with consumption. Total urinary Mg('++) excretion in alcohol-exposed mice is significantly elevated in withdrawal while no change in total Ca('++) or Zn('++) excretion was noticed.Magnesium replacement therapy at 250 or 350 mg/kg/day for five days did not significantly alter withdrawal symptoms of alcohol-exposed animals. Additionally, no significant difference in plasma or whole brain Mg('++) concentration was noted.Collectively, these data indicate that ethanol-generated respiratory alkalosis plays little or no role in the onset or development of withdrawal symptoms in mice and rats following chronic ethanol intoxication. Moreover, the lack of correlation between acid-base profiles and divalent cation changes and the inability of magnesium replacement therapy to alter whole brain magnesium concentrations suggest a minor or no role of whole brain ion changes in the development of withdrawal.

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