Delta-sleep-inducing peptide potentiates anticonvulsive activity of valproate against metaphit-provoked audiogenic seizure in rats.
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.
Hrncić
Dragan
D
Laboratory of Neurophysiology, Department of Physiology, School of Medicine, University of Belgrade, Serbia and Montenegro.
Stanojlović
Olivera
O
Zivanović
Dragana
D
Susić
Veselinka
V
D000161:Acoustic Stimulation / Q000009:adverse effects; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D003701:Delta Sleep-Inducing Peptide / Q000627:therapeutic use*; D004338:Drug Combinations; D020195:Epilepsy, Reflex / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009048:Motor Skills / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000627:therapeutic use*; D010622:Phencyclidine / Q000009:adverse effects / Q000031:analogs & derivatives; D051381:Rats; D017208:Rats, Wistar; D014635:Valproic Acid / Q000627:therapeutic use*
D000927:Anticonvulsants; D004338:Drug Combinations; D018377:Neurotransmitter Agents; D014635:Valproic Acid; D003701:Delta Sleep-Inducing Peptide; C044705:metaphit; D010622:Phencyclidine