Concentrations of free amino acids in brains of mice of different strains during the physical syndrome of withdrawal from alcohol.

Chronic administration of ethanol by inhalation to 3 different strains of mice (DBA/2, C57/BL and TO, Swiss) was adjusted to produce similar concentrations of ethanol in blood of mice of each strain. After 10 days of administration of ethanol in this way all mice were withdrawn from ethanol. Great differences were observed in the severity of the ethanol physical withdrawal syndrome. That of the DBA/2 strain included spontaneous convulsions and some deaths. The C57/BL strain exhibited almost no physical signs of withdrawal. Mice of the TO, Swiss strain were intermediate between these two extremes. The concentrations of free amino acids in brain were similar in all strains in the absence of drug treatment with the exception of GABA (higher in the DBA strain) and glycine (lower in the C57 strain) concentrations. After the chronic administration of ethanol, GABA and proline concentrations were significantly reduced in the DBA and TO strains, but not significantly affected in C57 mice. In addition DBA mice showed a significant and prolonged increase in aspartate concentrations during the period of ethanol withdrawal; aspartate concentrations in the other strains were affected less. Differences between strains were also observed in the alteration of serine, alanine and isoleucine concentrations produced by chronic administration of ethanol. These results provide further evidence for the hypothesis that alterations of concentrations of free amino acids in brain may play a part in the behavioural changes which form the physical syndrome of withdrawal from ethanol. Genetic differences in susceptibility to physical dependence on ethanol may be determined by differences in the biochemical response of the brain to chronic ethanol administration.