A TACHYKININ NK1 RECEPTOR ANTAGONIST, CP-122,721-1, ATTENUATES KAINICACID-INDUCED SEIZURE ACTIVITY

Substance P (SP) can play an important role in neuronal survival. To a nalyze the role of SP in excitotoxicity, kainic acid (KA) was administ ered to rats and in situ hybridization was used to analyze the levels of the SP encoding preprotachykinin-A (PPT-A) mRNA in striatal and hip pocampal subregions 1, 4, and 24 h and 7 days after KA. In striatum an d piriform cortex, PPT-A mRNA peaked 4 h after KA while in hippocampus , levels peaked after 24 h. KA caused seizures and neuronal toxicity a s indicated by a reduction of the number of neurons in the hippocampal CA1 subregion after 7 days. KA was later administered alone or follow ing pretreatment with the tachykinin NK1 receptor antagonist CP-122,72 1-1 (0.3 mg/kg). The pretreatment decreased seizure activity and a neg ative correlation was found between seizure activity and survival of C A1 neurons. Conclusively, treatment with CP-122,721-1 has a seizure in hibiting property and may possibly counteract KA-induced nerve cell de ath in CA1. (C) 1998 Elsevier Science B.V. All rights reserved.