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Effect of aminooxyacetic acid, thiosemicarbazide and haloperidol on the metabolism and half-lives of glutamate and GABA in rat brain

1973; Elsevier BV; Volume: 22; Issue: 1 Linguagem: Inglês

10.1016/0006-2952(73)90259-1

1873-2968

G.G.S. Collins,

GABA and Rice Research

The activity of the enzymes glutamate decarboxylase (GAD) and GABA-2-oxoglutarate transaminase (GABA-T), the endogenous GABA and glutamate levels and the half-lives (t12 values) of radioactive GABA and glutamate have been measured in the brains of untreated rats and in those injected with aminooxyacetic acid (AOAA), thiosemicarbazide (TSC) and haloperidol. The effect of the drugs in vitro on a purified preparation of glutamate dehydrogenase (GDH) was also measured. AOAA profoundly inhibited GABA-T, did not inhibit GAD and in in vitro experiments activated GDH. Brain glutamate levels were unaffected by the drug as was the half-life for glutamate. Brain GABA levels were elevated after AOAA and the rate of disappearance of radioactive GABA slowed. TSC did not significantly alter either GABA or glutamate brain levels but did significantly inhibit GAD and GDH activities. In addition, TSC had no effect on the half-life of either GABA or glutamate. Haloperidol was an effective inhibitor of GDH in vitro and reduced brain glutamate concentrations in vivo. Moreover, the rate of disappearance of radioactive GABA was increased whereas that of glutamate was decreased. The drug had no effect on GAD and GABA-T activities or on brain levels of GABA. It is suggested that the behavioural effects of haloperidol might in part be due to actions on the metabolism of GABA and glutamate. Interaction of TSC with glutamate metabolism might be a factor in seizure-provoking activity of the drug.