Inhibitory influence of morphinans on ictal and interictal EEG changes induced by cortical application of penicillin in rabbits: A comparative study with NMDA antagonists and pentobarbitone

Abstract

The effects of dextrorphan (DX) and dextromethorphan (DM) were tested using the electroencephalogram (EEG) and behavioral effects induced by topical cortical application of penicillin in rabbits. For comparison, the influence of the NMDA antagonists, dizocilpine (MK 801) and 3-((±-2-carboxypiperazine-4-yl)propyl-1-phosphonic acid (CPP), and of pentobarbitone was investigated. Intracortical injection of 500 IU of penicillin produced an EEG spiking followed by a repeated generalization of the electrical and behavioral symptoms. Within a few minutes, DX (5–15 mg/kg, IV) or pentobarbitone (5–10 mg/kg, IV) reduced dose dependently and significantly (p < 0.01) the interictal and ictal EEG and behavioral effects elicited by cortical injection of 500 IU of penicillin. Higher doses of pentobarbitone (20 mg/kg, IV) but not of DX (20 mg/kg, IV) completely blocked the ictal behavioral and EEG effects elicited by cortical injection of 500 IU of penicillin. Within a few minutes, MK 801 (0.1–0.2 mg/kg, IV) or CPP (10–20 mg/kg, IV) reduced dose dependently and significantly (p < 0.01) the ictal EEG and behavioral effects elicited by cortical injection of 500 IU of penicillin, while they did not affect the penicillin-induced interictal EEG changes. Higher doses of MK 801 (0.3 mg/kg, IV) completely blocked the ictal behavioral and EEG effects elicited by cortical injection of 500 IU of penicillin. Within a few minutes, DM (10–20 mg/kg, IV) blocked the behavioral effects, but failed to affect either the interictal or the ictal EEG effects induced by cortical injection of 500 IU of penicillin. The data promote an involvement of NMDA receptors in the electrical and behavioral generalization of the epileptiform activity elicited by penicillin in rabbits. The results also indicate that morphinans might be successfully used for the acute treatment of epileptic and convulsive phenomena.