Simultaneous monitoring of the seizure-related changes in extracellular glutamate and γ-aminobutyric acid concentration in bilateral hippocampi following development of amygdaloid kindling

Abstract

We simultaneously monitored the seizure-related changes in extracellular hippocampal glutamate (Glu) and gamma-aminobutyric acid (GABA) concentration in brain dialysates in order to clarify the role of Glu and GABA in the development of kindling. Brain dialysates were collected every 5 min from 10 min prior to 80 min after stimulus in the three developing conditions consisting of pre-kindling state, stage 3 (C-3), and five consecutive stage 5 (5*C-5) following kindling in the same rat. Extracellular Glu level increased rapidly, lasting for only 5 min after stimulus. The post-stimulus ratio of Glu increase in partially kindled rats (C-3) was 2.5-3.5 times of the baseline, and in fully kindled rats it was about 5 times of the baseline. Extracellular GABA concentration enhanced gradually, reaching a plateau level at 15-20 min and lasting for several hours after stimulus at each stage. The enhancement of GABA level was about 1.5 times of the baseline in partially kindled stage, and was about 2.5 times of the baseline in fully kindled stage. There was no significant difference between the two hemispheres with respect to either the time-course or the magnitude of Glu and GABA increase respectively. These data show that progressive, transient and stimulus-induced enhancement of extracellular Glu levels combined with long-lasting elevation of extracellular GABA levels in the bilateral ventral hippocampi results in imbalance between the excitatory and inhibitory neuronal systems, causing excessive propagation of seizure activity, culminating in the secondary generalized seizure of amygdaloid kindling.