Valproate and delta-sleep peptide display high efficacy against metaphit-induced audiogenic seizure in rats

Abstract

The effects of valproate (VPA) and delta sleep-inducing peptide (DSIP) on metaphit-induced generalized, audiogenic seizure in adult rat males were compared. The animals were i.p. injected with: 1. Saline; 2. metaphit (mp, 10 mg kg-1); 3. metaphit (10 mg kg-1) and 8 h later with DSIP (0.1, 0.2, 0.4 or 1.0 mg kg-1), 4. metaphit (10 mg kg-1) and 8 h later with VPA (50, 75 or 100 mg kg-1); 5. DSIP alone (1.0 mg kg-1) and 6. VPA, alone (100 mg kg-1). The rats were exposed to sound stimulation at hourly intervals and the behavior and EEG were analyzed. The EEG signals in metaphit rats appeared as a sleep-like pattern and spike-wave complexes with increased power spectra. Valproate and DSIP reduced the incidence of seizure and prolonged duration of latency in a dose-dependent manner. ED50 of valproate in the 1st hour after administration was 63.19 mg kg-1 and that of DSIP 3.19 mg kg-1 four hours after injection. This suggests that VPA, reached a peak of action immediately after the application, while DSIP had a prolonged action, mildly reducing, but not abolishing metaphit seizure. None of the applied VPA and DSIP doses eliminated the metaphit-provoked EEG signs of epileptiform activity. © 2006 Akadémiai Kiadó, Budapest.