Delta sleep-inducing peptide and its analogues alleviate the severity of metaphit-induced audiogenic seizures in rats

Abstract

We investigated the potential of delta sleep-inducing peptide (DSIP) and its analogue DSIP-12 (a nonapeptide with alanine in position 2 of DISP molecule substituted by beta-alanine) and tetrapeptide analogue DSIP1-4, to antagonize metaphit(1-1 (3-isothiocyanatophenl)-cvyclohexyl piperidine) induced generalized reflex audiogenic seizures in adult male Wistar albino rats. Five groups of adult male Wistar rats were intraperitoneally treated with: (1) saline; (2) metaphit: (3) metaphit + DSIP, (4) metaphit + DSIPI-4 and (5) metaphit + DSIP-12. To examine the blocking effects of DSIP and its analogues on fully developed metaphit seizures, in the last three groups they were administered 8h after metaphit injection. The rats were stimulated using an electric bell (1003 dB, 5-8 kHz, 60 s) one hour after metaphit injection and afterwards at hourly intervals during the experiment. For EEG recordings and power spectra three gold-plated screws were implanted into the skull. In metaphit-treated animals EEGs appeared as polyspikes and spike-wave complexes, while power spectra were increasing. The incidence and severity of netaphit-induced audiogenic seizures reached a peak value at 7-12 h after injection. Both DSIP and DSIP analogues significantly increased power spectra of delta waves and decreased the incidence of seizures, as well as mean seizure grade and tonic component of metaphit-induced convulsions. Taken together, these results suggest that DSIP and its analogues should be considered as potential antiepileptic agents.