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Published on: December 22, 2016
Interaction of Delta sleep-inducing peptide and valproate on metaphit audiogenic seizure model in rats
Olivera Stanojlović1, Dragan Hrncić, Aleksandra Rasić
1Institute of Physiology, School of Medicine, University of Belgrade, Visegradska 26/II, Belgrade 11000, Serbia. solja@afrodita.rcub.bg.ac.yu
Abstract:
Effects of valproate (VPA), a conventional antiepileptic drug and natural delta sleep-inducing peptide (DSIP) on metaphit (1-[1-(3-isothiocyanatophenyl)-cyclohexyl]-piperidine)-induced audiogenic reflex epilepsy were studied. For the purpose of the study, valproate in the doses of 50 or 75 mg/kg and DSIP (1.0 mg/kg) was i.p. injected either alone or in combination to adult Wistar male rats with fully developed metaphit seizures after eight audiogenic testing. The animals were stimulated using an electric bell (100 +/- 3 dB and 5-8 kHz, for 60 s) 60 min after metaphit injection and afterwards at hourly intervals during the experiment. For EEG recording and power spectra analysis, three gold-plated screws were implanted into the scull. In EEGs of metaphit-treated animals polyspikes, spike-wave complexes and sleep-like patterns were recorded, while the power spectra were increased. Combined treatment of metaphit-induced seizures with valproate and DSIP was more effective than drugs alone especially during 4 h after administration. None of the applied dose combinations eliminated the EEG signs of metaphit-provoked epileptiform activity. Taken together, the results of the present study suggest that the combinations of valproate and DSIP should be considered as beneficial polytherapy in metaphit model of epilepsy.
Insights
Valproate (VPA) and delta sleep-inducing peptide (DSIP) combination therapy showed benefits in a metaphit-induced epilepsy model in rats. This polytherapy was more effective than individual drugs in reducing seizure activity.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Epilepsy is a neurological disorder characterized by recurrent seizures.
- Metaphit is a drug used to induce audiogenic reflex epilepsy in animal models.
- Valproate (VPA) is a conventional antiepileptic drug, and delta sleep-inducing peptide (DSIP) is a naturally occurring peptide.
Purpose of the Study:
- To investigate the effects of valproate (VPA) and delta sleep-inducing peptide (DSIP) on metaphit-induced audiogenic reflex epilepsy.
- To evaluate the efficacy of VPA and DSIP as monotherapy and in combination for epilepsy treatment.
Main Methods:
- Adult Wistar male rats were used, and metaphit was administered to induce seizures.
- Animals received VPA (50 or 75 mg/kg) and/or DSIP (1.0 mg/kg) via intraperitoneal injection.
- Audiogenic stimulation was applied using an electric bell, and electroencephalogram (EEG) recordings were analyzed.
- EEG data were analyzed for power spectra to assess epileptiform activity.
Main Results:
- Metaphit-induced seizures in rats were associated with increased power spectra and specific EEG patterns like polyspikes and spike-wave complexes.
- Combined treatment with VPA and DSIP demonstrated greater efficacy in managing seizures compared to either drug alone, particularly within 4 hours post-administration.
- No tested combination completely abolished the EEG signs of metaphit-provoked epileptiform activity.
Conclusions:
- The combination of valproate and DSIP shows promise as a beneficial polytherapy for managing epilepsy in the metaphit-induced seizure model.
- Further research into VPA and DSIP combination therapy could lead to improved treatment strategies for certain epilepsy types.
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