GABA turnover in mouse brain: agreement between the rate of GABA accumulation after aminooxyacetic acid and the rate of disappearance after 3-mercaptopropionic acid

Abstract

GABA levels of the whole mouse brain were studied after in vivo inhibition of GABA synthesis by 3-mercaptopropionic acid (3-MPA, 100 mg/kg i.p.) and of GABA degradation by aminooxyacetic acid (AOAA, 3.8-60 mg/kg i.v.). The influence of 3-MPA on GABA levels was investigated in brains where postmortal GABA accumulation was allowed to occur and in brains where this phenomenon was avoided by very rapid dissection and homogenization of the brain in acid (within 50 sec after decapitation). The post-mortal GABA increase was blocked by 86% after injection of 3-MPA and 3 min before decapitation. In the group where the postmortal accumulation was avoided by very rapid homogenization of the brain in acid, GABA levels decreased by 15% within 2 min after 3-MPA (mean turnover time = 14 min). From 2 to 4 min the GABA concentration remained stable at this decreased level. GABA accumulation after AOAA was maximal after a dose of 7.5 to 15 mg/kg. i.v. Doses higher than 60 mg/kg always produced convulsions. The phase of most rapid accumulation of GABA after AOAA indicates a mean turnover time of about 10 min. The first rapid phase of accumulation was followed by a slower phase. It is probable that the turnover time of whole mouse brain GABA is approximately 10-14 min. It is also concluded that AOAA in a dose of around 15 mg/kg i.v. hardly can inhibit GAD in vivo in the mouse brain and that this dose, by this route of administration, could be used for studies of GABA synthesis in vivo in the mouse.