Metyrapone, an inhibitor of corticosterone synthesis, blocks the kainic acid-induced expression of HSP 70

It is shown in the present study that metyrapone (100 mg/kg), an inhibitor of corticosterone synthesis, given twice, 30 min before and 6 h after kaini c acid (10 mg/kg) administration, blocks the kainic acid-evoked induction o f heat shock proteins 72 kDa (HSP 70). Specifically, it was observed that m etyrapone completely prevented kainic acid-induced appearance of HSP 70 in the rat amygdala, habenula, parietal cortex, and significantly decreased th e number of HSP 70-positive neurons in the CA1, CA3, and CA4 subregions of hippocampus. The reduction in HSP 70 induction was paralleled by a complete prevention of the kainic acid-induced rise in the circulating corticostero ne level by metyrapone; however, in applied doses metyrapone evoked slight enhancement of blood corticosterone. Despite the fact that metyrapone block ed/attenuated the kainic acid-evoked induction of HSP 70, its administratio n did not affect the behavioral effects of kainic acid, regarded as "limbic status epilepticus." It is concluded that the blockade of corticosterone s ynthesis might have neuroprotective effects in the pathological states asso ciated with the overstimulation of glutamatergic receptors. (C) 2000 Wiley- Liss, Inc.