Regulation of gamma-aminobutyric acid metabolism in different brain structures by cholinergic and adrenergic drugs.

The influence of cholinergic and dopaminergic drugs has been studied on the metabolism of GABA by measuring the levels of GABA and glutamate and the activity of glutamic acid decarbosylase and GABA-aminotransferase in mouse and rat brain and in some rat brain regions. Muscarinic agonists (oxotremorine, arecoline) induce a rapid decrease of GABA level and an increase of its destruction, indicative of an increased activity of GABA synapses in basal ganglia and brain stem. Minor changes in GABA metabolism are observed in cerebral cortex and cerebellum. On the other hand, hemicholinium-3 and the muscarinic antagonist amizyle reduce the activity of GABA structures. Amizyle also abolishes the influence of muscarinic drugs on GABA metabolism. Most dopaminergic drugs (apomorphine, L-DOPA, CB-154, fusaric acid, 6-hydroxydopamine, haloperidol) fail to influence GABA metabolism in whole brain and in basal ganglia. However, amantadine decreases GABA metabolism and clozapine inhibits its destruction and increases its level (like aminooxyacetic acid). These data indicate that cholinergic neurons have a stimulant influence on the functional activity of GABA neurons.