Antiepileptic activity of delta sleep-inducing peptide and its analogue in metaphit-provoked seizures in rats.
OBJECTIVE
Previous studies have shown that humoral, endogenous and somnogenic, delta sleep-inducing peptide (DSIP) has influence on insomnia, pain, adaptation to stress, epilepsy, etc. We investigated the potential of DSIP and its analogue DSIP-12 (a nonapeptide with alanine in position 2 of DSIP molecule substituted by beta-alanine) to antagonize metaphit (1-[1(3-isothiocyanatophenyl)-cyclohexyl]piperidine) induced generalized, reflex audiogenic seizures in adult male Wistar albino rats.


METHODS
The rats divided in four groups received (i.p.): saline; metaphit; metaphit+DSIP; and metaphit+DSIP-12, respectively. Metaphit-treated animals displaying seizure in eight previous tests received DSIP or DSIP-12 and afterwards audiogenic stimuli were applied at hourly intervals for the next 30 h. The animals were exposed to sound stimulation 60 min after metaphit administration and further on at hourly intervals. Incidence and severity of seizures were behaviorally analyzed. Selected EEGs and power spectra were recorded and analyzed.


CONCLUSIONS
Metaphit led to hypersynchronous epileptiform activity (polyspikes and spike-wave complexes) and increased power spectra 0.5-30 h after the treatment. Severity of metaphit seizures increased with time to reach the peak 7-12 h after injection. DSIP and DSIP-12 significantly (*P<0.05 and **P<0.01) increased in delta and theta frequency bands and decreased the incidence, mean seizure grade and duration of metaphit convulsions. The results suggest that DSIP and DSIP-12 may be considered as potential antiepileptics in the animal model, DSIP-12 being more efficient than DSIP.
Stanojlović
Olivera P
OP
Department of Physiology, School of Medicine, University of Belgrade, 11000 Belgrade, Visegradska 26/II, Serbia. maxol@eunet.yu
Zivanović
Dragana P
DP
Mirković
Slobodan D
SD
Mikhaleva
Inessa I
II
D000161:Acoustic Stimulation / Q000009:adverse effects; D000818:Animals; D001522:Behavior, Animal; D003701:Delta Sleep-Inducing Peptide / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004347:Drug Interactions; D004569:Electroencephalography / Q000187:drug effects; D020195:Epilepsy, Reflex / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D005625:Frontal Lobe / Q000187:drug effects / Q000503:physiopathology / Q000528:radiation effects; D008297:Male; D013058:Mass Spectrometry; D010622:Phencyclidine / Q000031:analogs & derivatives*; D051381:Rats; D011920:Rats, Inbred WF; D011930:Reaction Time / Q000187:drug effects / Q000528:radiation effects; D013997:Time Factors
D003701:Delta Sleep-Inducing Peptide; C044705:metaphit; D010622:Phencyclidine