EFFECT OF DRUGS ON RAT BRAIN, CEREBROSPINAL FLUID AND BLOOD GABA CONTENT

Abstract

AbstractAcute administration of GABA transaminase inhibitors to rats results in a dose‐dependent increase in both brain and blood GABA content and administration of isonicotinic acid hydrazide (INH), at a dose which decreases the amount of brain GABA, also lowers blood levels of this amino acid. Chronic treatment (10 days) with INH (20mg/kg), y‐acetylenic‐GABA (10 mg/kg) or aminooxyacetic acid (AOAA) (10 mg/kg) results in a significant elevation in both rat brain and blood GABA concentrations. At the doses studied, only AOAA caused a significant elevation in CSF GABA content. Co‐administration of pyridoxal phosphate (2 mg/kg) blocks the chronic INH‐induced rise in blood GABA but does not affect the increase in brain content of this amino acid. Chronic administration of di‐n‐propylacetate (20 mg/kg) did not significantly alter brain, blood or CSF GABA levels. The results suggest that, under the proper conditions, changes in blood GABA levels after administration of inhibitors of GABA synthesis or degradation may be an indirect indicator of changes in the brain content of this amino acid. Blood GABA determinations may be useful for studying the biochemical effectiveness of GABA transaminase inhibitors in man.