EFFECTS OF CHRONIC TREATMENT WITH AMINO‐OXYACETIC ACID OR SODIUM n‐DIPROPYLACETATE ON BRAIN GABA LEVELS AND THE DEVELOPMENT AND REGRESSION OF COBALT EPILEPTIC FOCI IN RATS

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Abstract
Abstract– Acute treatment of cobalt‐induced epilepsy in rats with amino‐oxyacetic acid (20‐60 mg/kg intraperitoneally) resulted in a short period (30‐90 min) of epileptic spike suppression. In contrast sodium n‐dipropylacetate (100‐400 mg/kg intraperitoneally) had no effect on spike frequencies. Chronic treatment of cobalt epileptic rats with amino‐oxyacetic acid (2.5‐10 mg/kg intraperitoneally daily) or sodium n‐dipropylacetate (200‐400 mg/kg intraperitoneally daily) elevated brain GABA concentrations significantly and reduced brain glutamate decarboxylase activity relative to control saline‐injected cobalt epileptic rats. Brain γ‐aminobutyrate aminotransferase activity was significantly reduced by chronic treatment with amino‐oxyacetic acid, whereas chronic sodium n‐dipropylacetate had no effect on brain γ‐aminobutyrate aminotransferase activity although elevating brain GABA. Amino‐oxyacetic acid (2.5‐10 mg/kg intraperitoneally per day) reduced the frequency of epileptic spikes in the secondary foci of cobalt epileptic rats. The anticonvulsant action of amino‐oxyacetic acid was most marked at 5 mg/kg intraperitoneally where a secondary focus failed to develop in treated cobalt epileptic rats. However, there was no simple relationship between the elevation of brain GABA and the anticonvulsant action of amino‐oxyacetic acid. Thus focal GABA was higher in rats given intraperitoneal amino‐oxyacetic acid (10 mg/kg) but the anticonvulsant action of amino‐oxyacetic acid was less marked at this dose. Sodium n‐dipropylacetate (200‐400 mg/kg intraperitoneally per day) had no long‐term anticonvulsant action in this model of epilepsy. It is concluded that the anticonvulsant action of sodium n‐dipropylacetate, and probably that of amino‐oxyacetic acid, is not likely to be mediated through a mechanism involving elevation of brain GABA.