PICROTOXIN AND PENTYLENE TETRAZOLE INDUCED SEIZURE ACTIVITY IN PYRIDOXINE-DEFICIENT RATS

Computerized electroencephalography and thalamic ventro-posterior late ral (VPL) unit activities were recorded from pyridoxine-deficient and pair-fed pyridoxine-supplemented adult male rats. Pyridoxine-deficient animals exhibited slow electroencephalograms (EEG) represented by the dominance of delta activity and reduced seizure thresholds to local ( VPL) application of either picrotoxin or pentylene tetrazole. Frequenc y and amplitude of thalamic VPL unit activity were significantly reduc ed in pyridoxine-deficient rats as compared to pyridoxine-supplemented controls. Pyridoxine-deficient rats exhibited irregular unit activity with frequent bursts and electrosilent periods in response to local ( VPL) picrotoxin or pentylene tetrazole microinjections. They also exhi bited severe seizure discharge activity of prolonged duration at any g iven dose of either picrotoxin or pentylene tetrazole. This was repres ented by significantly increased burst frequency, burst duration and r educed seizure latencies. Unit activity was transformed into burst dis charge activity with intermittent electrosilent zones during picrotoxi n or pentylene tetrazole epileptogenesis. Cerebral gamma aminobutyric acid (GABA) level was reduced and glutamate concentration increased in pyridoxine-deficient rats when compared with pyridoxine-supplemented controls. Local (VPL) microinjection of GABA or pyridoxine induced neu ronal recovery in both convulsant-treated normal and pyridoxine-defici ent rats. Neuronal recovery was however delayed in pyridoxine-deficien t rats. Neuronal recovery was associated with a significant increase i n EEG background frequency and reduction in delta frequencies in the E EG records of both normal and pyridoxine-deficient rats. Reduced seizu re threshold and delayed neuronal recovery are related to the signific antly reduced brain regional GABA and elevated glutamate levels in pyr idoxine-deficient rats.