Effects of the glutamic acid decarboxylase inhibitor 3-mercaptopropionic acid on the synthesis of brain GABA in vivo and postmortally.

The effects of the glutamic acid decarboxylase inhibitor 3-mercaptopropionic acid (MPA) on the concentration of GABA in the mouse brain were studied. MPA completely inhibited the postmortem increase in GABA. This effect was used in order to achieve a maximal inhibition of the GABA synthesis in vivo during 67.5 minutes before killing by giving the drug repeatedly (50 mg/kg + 6 X 10 mg/kg i.p.) to mice pretreated with chloral hydrate (100 mg/kg i.p., 65 min before killing). Such a treatment with MPA markedly reduced the accumulation of GABA following inhibition of the GABA transaminase by aminooxyacetic acid but it did not change the endogenous concentration of GABA. This discrepancy might be due to inhibition of the impulse--evoked release of GABA following MPA.