The effect of delta-sleep-inducing peptide (DSIP) on the anticonvulsive activity of a nonprotective valproate (VPA) dose in a metaphit model of generalized, reflex audiogenic seizures in adult Wistar rats was studied. The animals that received metaphit (10 mg/kg) were exposed to audiogenic stimulation (100 ± 3 dB, 60 s) at hourly intervals. Metaphit-treated rats displaying seizures in 8 previous tests were i.p. injected with VPA (50 mg/kg) or DSIP (1.0 mg/kg) or their combination. Latency to seizure was behaviorally assessed. The EEGs and power spectra were recorded and analyzed. Neurotoxicity was evaluated by the chimney test. DSIP or VPA alone expressed no significant effect on the latency duration, but their combination significantly prolonged latency to seizure during 6 h after injection, while inducing no significant motor impairment. Neither the applied drugs nor their combination abolished metaphit-provoked EEG epileptiform activity. The results show that DSIP potentiated anticonvulsive effects of a nonprotective VPA dose in a metaphit model of audiogenic seizures without influencing its neurotoxicity.

1 figure)This study examined the effects of clozapine on sleep-wakefulness profile in cats prepared for chronic recording of sleep. Clozapine in single dose (Lp.) of 5 mg/kg drastically reduced slow-wave sleep (SWS) and paradoxical sleep (PS), while wakefulness and drowsy pattern were increased. These changes lasted approximately 24 h and were followed by sleep recovery. PS had a priority of recovery. Some similarities between clozapine effects on sleep in cat and human were mentioned. Archives of Physiology and Biochemistry Downloaded from informahealthcare.com by McMaster University on 12/03/14 For personal use only. physiology, Endocrinology, Episodes, Dreams, Epilepsy and Intracranial Pathology (LEVIN, P. & KOELLA, W. P., eds) p. 31 1-315. Karger, Basel. Brit. J. Pharmacol. 46, 736-140. SUSIC, V. & KOVAEEVI~, R. (1974) Brain Res. 65, 427-441. Veselinka SUSIC Fiziolski Institut Medicinskog Fakulteta 26, ViSegradska, 1 1O00, Beograd, Jugoslavija Archives of Physiology and Biochemistry Downloaded from informahealthcare.com by McMaster University on 12/03/14 For personal use only.

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.