Drug-induced changes in the GABA content of nerve terminals determined using a synaptosomal model

Abstract

Previous work by the authors has shown that the GABA content of synaptosomal-enriched fractions is stable during the preparation of the organelles and that changes in this parameter are therefore likely to give a meaningful reflection of changes in the GABA content of nerve endings. Use of the synaptosomal model indicated that convulsant drugs which induce quite different changes in whole brain GABA levels bring about similar decreases in the GABA content of synaptosomal-enriched fractions prepared from the brains of mice at the onset of seizures. Anticonvulsant drugs which elevate brain GABA levels and which have little or no effect on GAD activity show a good correlation between the elevation in synaptosomal GABA levels and the increase in whole brain GABA content. A similar relationship is not found when the drugs are also strong inhibitors of GAD activity. Although seizures can occur when the GABA content of nerve endings (synaptosomes) is above normal, such as after treatment with GABA-elevating agents, the percent decrease in GABA content due to the convulsant agents is similar.