Systemic administration of kainic acid increases GABA levels in perfusate from the hippocampus of rats in vivo.

Abstract

The ventral hippocampi of male, Fischer-344 rats were implanted with microdialysis probes and the effects of systemically administered kainic acid (KA) (8 mg/kg, s.c.) on the in vivo release of amino acids were measured for four hours after administration. In order to measure GABA release in vivo, gamma-vinyl-GABA (GVG), an irreversible inhibitor of GABA transaminase, was injected intrahippocampally prior to perfusion. GVG pretreatment resulted in measurable levels of GABA in the perfusate without significant effects on the release of aspartate, glutamate, glutamine, glycine or taurine. Following GVG pretreatment systemic administration of KA produced a time-dependent increase in GABA, as well as all other amino acids except glutamine, which was initially decreased. These results show for the first time that systemically administered KA increases extracellular GABA levels, an effect previously reported only in vitro. These data suggest that prior to destruction of GABA-containing interneurons in the hippocampus, there is an increased activity of those GABA interneurons reflected as an increase in extracellular GABA levels.