PREVENTION OF KAINIC ACID-INDUCED LIMBIC SEIZURES AND FOS EXPRESSION BY THE GABA-A RECEPTOR AGONIST MUSCIMOL

Fos oncoprotein expression has been shown to be a sensitive marker for sequential neuronal activation in response to a specific stimulus. Th e present study investigated the effect of the gamma-aminobutyric acid (GABA)-A receptor agonist muscimol on kainic acid (KA)-induced limbic seizures and Fos expression in the rat forebrain. One hour after KA i njection, a substantial Fos expression was observed in the hippocampal dentate gyrus, whereas only a low level of Fos induction was seen in CA1-3 fields. Six hours post-injection a prominent increase of Fos exp ression occurred in most forebrain structures, including the whole hip pocampus. Following 0.5 mg/kg muscimol treatment a remarkable decrease of Fos expression occurred but only in the caudate putamen and core o f the accumbens nucleus. Treatment with 1 mg/kg muscimol led to furthe r significant decreases of Fos expression in CA1-3 pyramidal neurons a nd the disappearance of Fos induction in the cerebral cortex above the rhinal fissure, reticular thalamic nucleus, claustrum, fundus striati , ventral pallidum, septal nucleus, lateral habenular nucleus, and lat eral amygdaloid nucleus. When 2 mg/kg muscimol was injected, animals e xhibited 'absence seizures' instead of limbic seizures, and Fos expres sion in the hippocampus was effectively blocked. These results suggest that a reduction of GABAergic inhibition plays a crucial role not onl y in limbic seizure genesis in the dentate gyrus, but also in the seiz ure spread mechanism in many brain structures, among which the hippoca mpal CA1-3 fields are most markedly involved, less marked in the cereb ral cortex and some other structures, and least marked in the caudate putamen and core of the accumbens nucleus.