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Chronic ethanol consumption is a major risk factor for epilepsy, and seizures frequently occur during the withdrawal period. The aim of our study was to investigate effects of ethanol on lindane-induced seizures in rats. Male Wistar rats were injected i.p. with one of the following 5 treatments: (i) saline, (ii) dimethylsulfoxide, (iii) lindane (8 mg/kg) (L), (iv) ethanol in doses of 0.5 g/kg (E(0.5)), 1 g/kg (E(1)), and 2 g/kg (E(2)), and (v) groups that received ethanol 30 min before lindane (LE(0.5), LE(1), and LE(2)). Behavioral changes were described by using a descriptive scale as follows: 0, no response; 1, head nodding, lower jaw twitching; 2, myoclonic body jerks, bilateral forelimb clonus; 3, generalized tonic-clonic convulsions; 4, status epilepticus. The incidence of convulsions in the LE(2) group was significantly lower than the incidence in the L (p < 0.01) and LE(0.5) groups (p < 0.05). The median grade of convulsive behavior was significantly lower in the LE(2) (p < 0.01) and LE(1) groups (p < 0.05) compared with the L group. Latencies to the first seizure response were not significantly different among groups. ED50 of ethanol was 1.40 (1.19-1.65). Our findings suggest that ethanol decreased severity and incidence of lindane-induced seizures in a dose-dependent manner.

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.

Introduction: 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., Material and Methods: 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., Results: 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., Conclusion: Taken together, these results suggest that DSIP and its analogues should be considered as potential antiepileptic agents.

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.

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., (Copyright 2006 S. Karger AG, Basel.)