THE EFFECTS OF DEXTROMETHORPHAN ON KAINIC ACID-INDUCED SEIZURES IN THE RAT

Several studies have shown that dextromethorphan (DM) has both anticon vulsant and proconvulsant effects depending on the animal model. In th is study, we examined the effects of DM on three parameters associated with kainic acid (KA)induced seizures: cell loss in the hippocampus, increased AP-I DNA binding activity and increased c-Jun and fos-relate d antigen (FRA) expression. KA administration (8 mg/kg, ip) produced r obust behavioral convulsions lasting 4-6 hr. Pretreatment with DM (12. 5-75 mg/kg, po) 15 min before KA injections reduced the seizures as we ll as mortality in a dose-dependent manner. Histological studies revea led a severe loss of cells in the CA1 and CA3 fields of the hippocampu s in KA-treated rats. DM pretreatment also reduced this cell loss in a dose-dependent fashion. Biochemical studies showed that DM pretreatme nt also attenuated the KA-induced in crease of AP-1 binding activity a nd c-Jun/FRA expression in the hippocampus. These results indicate tha t DM is an effective antagonist of KA. (C) 1996 Intox Press Inc.