Effect of depth electrode implantation with or without subsequent kindlingon GABA turnover in various rat brain regions

Kindling is a chronic model of epilepsy characterized by a progressive incr ease in response to the same regularly applied electrical stimulus. The bio logical basis of the kindling phenomenon requires to be determined, but sev eral studies indicate that impairment of GABAergic inhibition may be involv ed. In the present experiments, GABA turnover was determined in vivo by the GABA aminotransferase (GABA-T) inhibition method in 13 brain regions in th ree groups of rats: (1) a group which was kindled via electrical stimulatio n of intra-amygdala electrodes and was sacrificed 36 days after the last fu lly kindled seizure for neurochemical determinations; (2) a group of implan ted but non-stimulated rats (sham control group) in which neurochemical mea surements were done at the same time after electrode implantation as in the kindled group; and (3) a group of non-implanted, naive control rats. Regio nal GABA levels were determined after vehicle injection as well as 30 and 9 0 min after administration of aminooxyacetic acid (AOAA) at a dose which co mpletely inhibits GABA-T. Compared to naive controls, prolonged electrode i mplantation in the amygdala induced a significant reduction of AOAA-induced GABA accumulation in amygdala, hippocampus, piriform cortex, olfactory bul b, frontal cortex, striatum, hypothalamus, tectum, and cerebellar cortex. I n view of the GABA hypothesis of kindling, reduced GABA turnover in respons e to electrode implantation would suggest that the implantation per se exer ts a pro-kindling effect, which was recently demonstrated in rats with intr aamygdala electrodes. However, amygdala kindling itself appeared to antagon ize the effect of electrode implantation in most regions. Thus, although, c ompared to naive controls, the predominant change in kindled rats was a dec rease 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 respons e to impaired postsynaptic GABAergic function. The data indicate that both electrode implantation and kindling significantly alter regional GABA turno ver, which might contribute to the pathophysiology of the kindling phenomen on. Furthermore, the data substantiate that the choice of adequate controls is critical in neurochemical and functional studies on the kindling phenom enon. (C) 1999 Elsevier Science B.V. All rights reserved.