Concentrations of free amino acids in brains of mice during the induction of physical dependence on ethanol and during the ethanol withdrawal syndrome.

Chronic administration of ethanol to mice by inhalation for 10 days produced physical dependence demonstrated by a characteristic syndrome of withdrawal. Free amino acid concentrations in whole brain were measured at intervals during the induction of dependence and during withdrawal. During the induction of dependence there was an initial increase in brain glycine, a sustained increase in brain tyrosine and reductions in brain GABA and proline. Serine and isoleucine concentrations were consistently reduced during the induction of dependence, but this change was not significant (P less than 0-05) at any single time interval studied. After the withdrawal of ethanol only the reductions in GABA and proline persisted during the withdrawal syndrome. In addition to these changes an increase in brain glycine concentration was observed during the ethanol withdrawal syndrome. In an attempt to discriminate between the immediate, metabolic effects of ethanol on central amino acid concentrations and those changes associated with the induction of ethanol dependence, the results were compared with those obtained when mice were exposed to a high concentration of ethanol vapour for 3 h. Although this produced similar blood ethanol concentrations, no evidence of physical dependence was observed. The changes in central amino acid concentrations differed from those seen during the induction of dependence in that no change in isoleucine concentration occurred, and that the reduced concentrations of GABA and proline very rapidly reverted to control values when ethanol was removed. The possible role of central amino acids in ethanol dependence is discussed.