1-AMINOCYCLOPROPANE-CARBOXYLIC ACID REDUCES NMDA-INDUCED HIPPOCAMPAL NEURODEGENERATION IN-VIVO

THE effect of systemic treatment with 1-aminocyclopropanecarboxylic ac id (ACPC), a partial agonist at the glycine site of the NMDA receptor, on convulsions and neurodegeneration induced by intrahippocampal inje ction of NMDA was investigated in mice. Five days after intrahippocamp al NMDA infusion, 80-100% pyramidal cell death was observed in the CA1 region of the hippocampus. Pretreatment with ACPC prevented the letha l effects of NMDA and significantly reduced seizure induction. ACPC re duced cell death to 40% of that induced by a dose of NMDA (6 nmol) tha t damaged 80% of hippocampal CA1 neurones in untreated animals. These findings provide further evidence that ACPC can reduce NMDA receptor f unction in vivo and suggest that partial agonists at the glycine site of the NMDA receptor complex may be useful anticonvulsant and neuropro tective agents.