Effect of diazepam and pentobarbital on aminooxyacetic acid-induced accumulation on GABA.

Abstract

Abstract— The effect of diazepam and pentobarbital on γ‐aminobutyric acid (GABA) levels, the aminooxyacetic acid (AOAA)‐induced accumulation of GABA, and the in vitro activity of l‐glutamate 1‐carboxyl‐lyase (EC 4.1.1.15) [GAD] were studied in various regions of rat brain. Diazepam increased GABA levels in the substantia nigra, diminished the AOAA‐induced accumulation of GABA in the caudate nucleus, cingulate, parietal and entorhinal cortex and had no effect on GABA accumulation in the pyriform and cerebellar cortex. After pentobarbital, GABA levels were elevated in the caudate nucleus but decreased in the parietal and pyriform cortex; the AOAA‐induced accumulation of GABA also diminished in all cortical regions studied. No correlation was found between the apparent changes in GABA synthesis, as estimated by accumulation after inhibition of 4‐aminobutyrate‐2‐oxoglu‐tarate (EC 2.6.1.19) [GABA‐T] with AOAA, and the changes in GABA levels induced by these drugs. The reduction in AOAA‐induced GABA accumulation after diazepam and pentobarbital treatment was most pronounced in regions which showed the greatest accumulation of GABA after AOAA administration. Neither diazepam nor pentobarbital administration affected the activity of GAD in homogenates of cingulate cortex. Chlorpromazine, at a dose which decreased spontaneous activity, enhanced the AOAA‐induced GABA accumulation in the cingulate cortex, suggesting that drug‐induced sedation is not necessarily associated with decreased GABA synthesis. While regional differences were observed in the effects of diazepam and pentobarbital on GABA synthesis, both agents appear to inhibit GABA synthesis in vivo and both do so, in at least some brain areas, at subsedative doses.