Decrease of glutamate decarboxylase activity after in vivo cortical infusion of γ-aminobutyric acid

Abstract

gamma-Aminobutyric acid (GABA) levels and the activity of glutamate decarboxylase were measured in homogenates of rat brain cortical tissue, at different times after chronic intracortical infusion of GABA in vivo during 2, 6 or 24 h. Cortical electrical activity was also recorded. As previously described, about 1 h after cessation of the infusion epileptic discharges were observed (GABA-withdrawal syndrome), which lasted for several days. At zero time after cessation of the infusion, before the appearance of seizures, GABA levels were increased 3-6-fold and glutamate decarboxylase activity was decreased 27-48% in the infused cortex, as compared to the contralateral cortex or to tissue from control intact rats. During epileptic discharges GABA levels gradually returned to normal values. In contrast, glutamate decarboxylase activity remained decreased during seizures and returned to normal only after recovery from the GABA-withdrawal syndrome. These results suggest that the persistent decrease in the activity of the decarboxylase is due probably to a lowered amount of the enzymatic protein, occurring as a consequence of a temporarily elevated intracellular GABA concentration. The decreased rate of GABA synthesis might be involved in the pathophysiology of the GABA-withdrawal syndrome.