EFFECT OF ISONICOTINIC-ACID HYDRAZIDE ON EXTRACELLULAR AMINO-ACIDS AND CONVULSIONS IN THE RAT - REVERSAL OF NEUROCHEMICAL AND BEHAVIORAL DEFICITS BY SODIUM VALPROATE

We have studied the effect of isonicotinic acid hydrazide (INH), a con vulsant agent, on the extracellular levels of amino acids in the hippo campus, and the effect of sodium valproate (VPA) administration in INH -treated rats. INH (250 mg/kg) caused a rapid and sustained decrease i n basal levels of GABA, and during this period convulsions of increasi ng severity were observed. Basal levels of glutamine, taurine, asparta te, and glutamate were unchanged by INH. When VPA was coadministered w ith INH, basal GABA levels were increased and no convulsions were obse rved. When transmitter release was evoked using 100 mM K+, the increas e in dialysate GABA observed in INH-treated animals was less than that seen in controls and convulsions increased in frequency. K+-evoked re lease of glutamate and aspartate tended to be higher following INH tre atment, and in the case of aspartate, this increase was significant. V PA reversed the changes in evoked release of glutamate and aspartate, and release of GABA was considerably greater than that seen in control or INH-treated rats. No drug effect on evoked changes in taurine or g lutamine level was seen. These are the first data to show decreased ex tracellular GABA in conjunction with convulsions in freely moving anim als in vivo.