Effect of depth electrode implantation with or without subsequent kindling on GABA turnover in various rat brain...

Kindling is a chronic model of epilepsy characterized by a progressive increase in response to the same regularly applied electrical stimulus. The biological basis of the kindling phenomenon requires to be determined, but several studies indicate that impairment of GABAergic inhibition may be involved. In the present experiments, GABA turnover was determined in vivo by the GABA aminotransferase (GABA-T) inhibition method in 13 brain regions in three groups of rats: (1) a group which was kindled via electrical stimulation of intra-amygdala electrodes and was sacrificed 36 days after the last fully kindled seizure for neurochemical determinations; (2) a group of implanted but non-stimulated rats (sham control group) in which neurochemical measurements were done at the same time after electrode implantation as in the kindled group; and (3) a group of non-implanted, naive control rats. Regional GABA levels were determined after vehicle injection as well as 30 and 90 min after administration of aminooxyacetic acid (AOAA) at a dose which completely inhibits GABA-T. Compared to naive controls, prolonged electrode implantation in the amygdala induced a significant reduction of AOAA-induced GABA accumulation in amygdala, hippocampus, piriform cortex, olfactory bulb, frontal cortex, striatum, hypothalamus, tectum, and cerebellar cortex. In view of the GABA hypothesis of kindling, reduced GABA turnover in response to electrode implantation would suggest that the implantation per se exerts a pro-kindling effect, which was recently demonstrated in rats with intraamygdala electrodes. However, amygdala kindling itself appeared to antagonize the effect of electrode implantation in most regions. Thus, although, compared to naive controls, the predominant change in kindled rats was a decrease in GABA turnover, this decrease was less marked than in sham controls. In thalamus and brainstem kindling markedly increased GABA turnover above the levels determined in both naive and sham controls, possibly in response to impaired postsynaptic GABAergic function. The data indicate that both electrode implantation and kindling significantly alter regional GABA turnover, which might contribute to the pathophysiology of the kindling phenomenon. Furthermore, the data substantiate that the choice of adequate controls is critical in neurochemical and functional studies on the kindling phenomenon.