Epileptiform Activity In Rats Research Articles

The interactions of nitric oxide and adenosine on penicillin-induced epileptiform activity in rats.

In this study, the influence of nitric oxide (NO) and adenosine systems on penicillin-induced epileptiform activity was examined in rats. NO donor, sodium nitroprusside (SNP, 50 micrograms per rat, i.c.v.) reduced the frequency but not the amplitude of epileptiform discharges. Non-selective NOS inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME, 100 micrograms per rat, i.c.v.) practically did not exert any effect on the spike frequency and amplitude. Adenosine (100 micrograms per rat, i.c.) reduced spike frequency but not the amplitude, whereas theophylline (100 micrograms per rat, i.c.v.) increased the mean spike frequency and amplitude of penicillin-induced epileptiform discharges. Co-injection of theophylline and L-NAME did not cause a further increase in the epileptiform activity compared with theophylline. When NO production was blocked with L-NAME, the inhibitory effects of adenosine were lost. The obtained results suggest that NO and adenosine may decrease penicillin-induced epileptiform activity in rats and that NO, at least in part, may mediate the anticonvulsant effect of adenosine.

The effect of co-administration of the NMDA blocker with agonist and antagonist of CB1-receptor on penicillin-induced epileptiform activity in rats

Although the activation of CB1-receptor by cannabinoids and block of NMDA receptors are known to decrease seizure severity in epilepsy models, the interaction between these systems remain elusive. Therefore, the present study was initiated to evaluate the possible interactions between cannabinoid compounds and NMDA receptor antagonist in the penicillin-induced epileptiform activity in rat. In the first set of experiments, 30 min after intracortical injection of penicillin, five different doses of memantine (3,5-dimethyl-1-adamantanamine hydrochloride, 1, 2.5, 5, 10 or 20mg/kg) were administered intraperitoneally (i.p.). In the second set of experiments, intracerebroventricular (i.c.v.) AM-251 [N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide], (0.25 μg) a CB1-receptor antagonist and ACEA (arachidonyl-2-chloroethylamide), (7.5 μg) a CB1-receptor agonist, were administered 15 min after memantine (i.p.) application. Memantine, NMDA receptor antagonist, at doses of 2.5 and 5mg/kg (i.p.) decreased the mean frequency of penicillin-induced epileptiform activity with a maximal effect at 5mg/kg. Memantine, at the lowest dose (1mg/kg, i.p.) and highest doses (10 and 20mg/kg, i.p.) did not change the frequency of epileptiform activity. ACEA, at a dose of 7.5 μg, also decreased the frequency of epileptiform activity, whereas AM-251, at a dose of 0.25 μg increased the frequency by causing status epilepticus-like activity. The best and earlier anti-epileptiform effects appeared in both the presence of memantine (5mg/kg, i.p.) and ACEA (7.5 μg, i.c.v.), which was blocked by CB1-receptor antagonist, AM-251. The results of the present study provide electrophysiologic evidence for an interaction between cannabinoid system and NMDA receptors, probably via NMDA-mediated Ca(2+) influx in the penicillin-induced epilepsy.

Interaction of leptin and nitric oxide pathway on penicillin-induced epileptiform activity in rats

The aim of the present study was to investigate the role of NO as a mediator of leptin action at the penicillin-induced epileptiform activity in rat. Thirty minutes after penicillin injection, leptin, at a dose of 1 µg, significantly increased the mean frequency of epileptiform activity without changing the amplitude. The effects of systemic administration of nitric oxide synthase (NOS) inhibitors, non-selective NG-nitro- l-arginine methyl ester (L-NAME), selective neuronal NOS inhibitor, 7-nitroindazole (7-NI) and NO precursor, l-arginine on the effects of leptin were investigated. The occurrence of anticonvulsant activity of 7-NI (40 mg/kg, i.p.) was significantly delayed in the presence of leptin (1 µg). The administration of L-NAME (60 mg/kg, i.p.), 30 min before leptin (1 µg) application, did not influence proconvulsant activity of leptin. The administration of l-arginine (1000 mg/kg, i.p.) 30 min before the effective dose of leptin (1 µg, i.c.v.) reversed the proconvulsant effects of leptin whereas the same dose of its inactive enantiomer, d-arginine (1000 mg/kg, i.p.) failed to influence the proconvulsant effect of leptin. The electrophysiological evidence of the present study suggests that neuronal NOS/NO pathway is involved in mediating leptin effects on penicillin-induced epileptiform activity.

Endothelial nitric oxide synthase activity involves in the protective effect of ascorbic acid against penicillin-induced epileptiform activity

Ascorbic acid and nitric oxide are known to play important roles in epilepsy. The aim of present study was to identify the involvement of nitric oxide (NO) in the anticonvulsant effects of ascorbic acid on penicillin-induced epileptiform activity in rats. Intracortical injection of penicillin (500, International Units (IU)) into the left sensorimotor cortex induced epileptiform activity within 2–5 min. Thirty minutes after penicillin injection, nitric oxide synthase (NOS) inhibitor, N G-nitro- l-arginine methyl ester ( l-NAME, 100 mg/kg), neuronal nitric oxide synthase (nNOS) inhibitor 7-nitroindazole (7-NI, 40 mg/kg), NO substrate, l-arginine (500 mg/kg) were administered with the most effective dose of ascorbic acid (100 mg/kg) intraperitoneally (i.p.). The administration of l-arginine significantly decreased the frequency of epileptiform activity while administration of l-NAME did not influence the mean frequency of epileptiform activity. Injection of 7-NI decreased the mean frequency of epileptiform activity but did not influence amplitude. Ascorbic acid decreased both the mean frequency and amplitude of penicillin-induced epileptiform activity in rats. The application of l-NAME partially and temporarily reversed the anticonvulsant effects of ascorbic acid. The results support the hypothesis of neuro-protective role for NO and ascorbic acid. The protective effect of ascorbic acid against epileptiform activity was partially and temporarily reversed by nonspecific nitric oxide synthase inhibitor l-NAME, but not selective neuronal nitric oxide synthase inhibitor 7-NI, indicating that ascorbic acid needs endothelial-NOS/NO route to decrease penicillin-induced epileptiform activity.

Electrophysiological effects of guanosine and MK-801 in a quinolinic acid-induced seizure model

Quinolinic acid (QA) is an N-methyl- d-aspartate receptor agonist that also promotes glutamate release and inhibits glutamate uptake by astrocytes. QA is used in experimental models of seizures studying the effects of overstimulation of the glutamatergic system. The guanine-based purines (GBPs), including the nucleoside guanosine, have been shown to modulate the glutamatergic system when administered extracellularly. GBPs were shown to inhibit the binding of glutamate and analogs, to be neuroprotective under excitotoxic conditions, as well as anticonvulsant against seizures induced by glutamatergic agents, including QA-induced seizure. In this work, we studied the electrophysiological effects of guanosine against QA-induced epileptiform activity in rats at the macroscopic cortical level, as inferred by electroencephalogram (EEG) signals recorded at the epidural surface. We found that QA disrupts a prominent basal theta (4–10 Hz) activity during peri-ictal periods and also promotes a relative increase in gamma (20–50 Hz) oscillations. Guanosine, when successfully preventing seizures, counteracted both these spectral changes. MK-801, an NMDA-antagonist used as positive control, was also able counteract the decrease in theta power; however, we observed an increase in the power of gamma oscillations in rats concurrently treated with MK-801 and QA. Given the distinct spectral signatures, these results suggest that guanosine and MK-801 prevent QA-induced seizures by different network mechanisms.

The effects of intracerebroventricular AM‐251, a CB1‐receptor antagonist, and ACEA, a CB1‐receptor agonist, on penicillin‐induced epileptiform activity in rats

Several results support the conclusion that the cannabinoid system has a role in generation and cessation of epileptic seizures. The aim of this study was to evaluate the effects of intracerebroventricular AM-251 [N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide], a CB1-receptor antagonist, and ACEA (arachidonyl-2-chloroethylamide), a CB1-receptor agonist, on penicillin-induced epileptiform activity in rats. In the first set of experiments, 30 min after penicillin injection, AM-251, at doses of 0.125, 0.25, 0.5, and 1 μg, was administered intracerebroventricularly (i.c.v.). In the second set of experiments, 30 min after penicillin injection, ACEA, at doses of 2.5, 5, 7.5, and 15 μg (i.c.v.), was administered. In the third set of experiments, AM-251, at doses of 0.125 and 0.25 μg (i.c.v.), was administered 10 min before ACEA (7.5 μg, i.c.v.) injection. ACEA, at a dose of 7.5 μg, significantly decreased the frequency of penicillin-induced epileptiform activity without changing the amplitude. ACEA, at doses of 2.5, 5, and 15 μg, had no impact on either frequency or amplitude of epileptiform activity. AM-251, at doses of 0.25 and 0.50 μg, significantly increased the frequency of epileptiform activity. AM-251, at a dose of 0.25 μg (i.c.v.), was the most effective in changing the frequency of penicillin-induced epileptiform activity, and it also caused status epilepticus-like activity. AM-251, at doses of 0.125 and 0.25 μg, 10 min before ACEA (7.5 μg), reversed the anticonvulsant action of ACEA. The results of the present study provide electrophysiologic evidence for the role of CB1 receptors in regulating the frequency of epileptiform activity in the model of penicillin-induced epilepsy. To elucidate the precise mechanism of cannabinoid action in the brain during seizure, more advanced electrophysiologic and neurochemical studies are required.

The effect of alpha-tocopherol in the acute ethanol intake and its withdrawal on penicillin-induced epilepsy.

The present study was designed to investigate the influence of acute ethanol intake and its withdrawal on the anticonvulsant effect of alpha-tocopherol in penicillin-induced epileptiform activity. Ethanol-treated rats received a daily dose of 3 g/kg or 9.0 g/kg of 30% ethanol solution for 3 days. Thirty minutes after penicillin injection (500 units, i.c.) the most effective dose of alpha-tocopherol (500 mg/kg) was administered intramuscularly (i.m.). Acute administration of ethanol, in a dose of 3 g/kg, did not change either frequency or amplitude of penicillin-induced epileptiform activity, while dose of 9 g/kg ethanol significantly decreased the mean frequency of penicillin-induced epileptiform ECoG activity in the ethanol-treated group. Ethanol (9 g/kg) withdrawal also caused an increase in the amplitude of epileptiform ECoG activity in the withdrawal group. The results suggest that acute administration of high dose ethanol (9 g/kg) and alpha-tocopherol have some limited anticonvulsive effects in penicillin-induced epileptiform activity in rats.

The role of nitric oxide in the inhibitory effect of ghrelin against penicillin-induced epileptiform activity in rat

Ghrelin, a gastric peptide with key action on food intake, has been recently recognized as a potential antiepileptic agent. In the present study, we investigated the involvement of nitric oxide in the effect of ghrelin on penicillin-induced epileptiform activity in rat. Thirty minutes after penicillin injection, ghrelin, at doses of 0.5, 1, 2 microg, was administered intracerebroventricularly (i.c.v.). Ghrelin, at a dose of 1 microg, significantly decreased the mean frequency of epileptiform activity without changing the amplitude whereas other doses of ghrelin (0.5 and 2 microg) did not alter either the mean of frequency or amplitude of epileptiform activity. The effects of systemic administration of nitric oxide synthase (NOS) inhibitors, non-selective N(G)-nitro-l-arginine methyl ester (l-NAME), selective neuronal NOS inhibitor, 7-nitroindazole (7-NI) and NO substrate, l-arginine on the anticonvulsive effects of ghrelin were investigated. The administration of l-NAME (60 mg/kg, i.p.), 15 min before ghrelin (1microg) application, reversed the anti-epileptiform effects of ghrelin whereas 7-NI (40 mg/kg, i.p.) did not influence it. The present study provides electrophysiological evidence that the intracerebroventricular injection of ghrelin has an inhibitory effect against epileptiform activity in the penicillin model of epilepsy. The anti-epileptiform activity of ghrelin was reversed by nonspecific nitric oxide synthase inhibitor l-NAME, but not selective neuronal nitric oxide synthase inhibitor 7-NI, indicating that ghrelin requires activation of endothelial-NOS/NO route in the brain.

Anticonvulsant effect of carnosine on penicillin-induced epileptiform activity in rats

Carnosine is a compound of naturally-occurring dipeptide that synthesized by the carnosine synthetase from β-alanine and l-histidine. Recent reports claim that carnosine plays an important role in the control of epilepsy but its involvement in anticonvulsant functions remains unknown. In this study, we investigated the effects of carnosine in a rat model of epilepsy using the intracortical penicillin injection method. Thirty minutes after penicillin injection, the doses of 125, 250, 500, 1000 mg/kg carnosine and 90 min before penicillin injection the dose of 500 mg/kg carnosine were administered intraperitoneally. The epileptiform activity was verified by electrocorticographic (ECoG) recordings. The mean spike frequency of penicillin-induced epileptiform activity was significantly decreased in all carnosine-treated rats when compared with those of penicillin-injected. The dose of 500 mg/kg for carnosine treated and pretreated rats was found to be the most effective dose in reducing the frequency of penicillin-induced epileptiform activity. There was no significant difference in the mean onset of epileptiform activity between penicillin and 500 mg/kg carnosine pretreated groups. These findings indicate that carnosine has an anticonvulsant effect on penicillin-induced epilepsy in rats. Thus, our data support the hypothesis that carnosine may be a potential anticonvulsant drug for clinical therapy of epilepsy in the future.

The role of nitric oxide in the anticonvulsant effects of pyridoxine on penicillin-induced epileptiform activity in rats

The present study was conducted to identify the role of nitric oxide (NO) in the anticonvulsant effects of pyridoxine hydrochloride on penicillin-induced epileptiform activity in rats. A single microinjection of penicillin (500 units) into the left sensorimotor cortex induced epileptiform activity within 2-4 min, progressing to full seizure activity lasting about 3-5h. Thirty minutes after penicillin injection, 20, 40, 80, and 160 mg/kg of pyridoxine hydrochloride was administered intraperitoneally (i.p.). Pyridoxine significantly reduced the frequency of penicillin-induced epileptiform activity. A low dose of pyridoxine (40 mg/kg) was the most effective in reducing both the frequency and amplitude of epileptiform activity. The effect of systemic administration of nitric oxide synthase (NOS) inhibitors, non-selective N(G)-nitro-L-arginine methyl ester (L-NAME), selective neuronal NOS inhibitor, 7-nitroindazole (7-NI) and NO substrate, L-arginine on anticonvulsive effects of pyridoxine was investigated. The administration of L-arginine (500 mg/kg, i.p.) and 7-NI (25 and 50 mg/kg, i.p.) significantly decreased the frequency of epileptiform electrocorticographical (ECoG) activity while administration of L-NAME (60 mg/kg, i.p.) and the inactive form of arginine (D-arginine) did not influence it. The administration of L-NAME (60 mg/kg, i.p.) 15 min before pyridoxine (40 mg/kg i.p.) application reversed the anticonvulsant effects of pyridoxine whereas 7-NI (25 and 50 mg/kg, i.p.) did not influence it. The same dose of its inactive enantiomer N(G)-nitro-D-arginine methyl ester (d-NAME) failed to reverse the anticonvulsant effects of pyridoxine. The administration of L-arginine (500 mg/kg, i.p.) did not affect the frequency of epileptiform ECoG activity in the pyridoxine administered group. L-arginine did not reverse the anticonvulsant effect of 7-NI in the penicillin and pyridoxine administered groups. The results of present study indicate that the inhibitory effect on the anticonvulsant activity of pyridoxine against penicillin-induced epileptiform activity was produced by L-NAME, not by 7-NI, and is probably not related to the decrease of NOS activity in the brain.

Anticonvulsant effects of damage to structures involved in seizure induction in rats exposed to soman

In nerve agent research, it is assumed that the regions from which seizure activity is triggered may offer clues for the designing of effective anticonvulsive therapy. In the present study, selective brain lesions were made to identify critical cholinergic pathways and seizure controlling areas involved in the induction of epileptiform activity in rats challenged with soman. The results showed that rats with bilateral aspiration lesion of the seizure controlling substrate, area tempestas (AT) in the piriform cortex, displayed marked anticonvulsant effects, whereas such effects were not seen when substantia nigra was destroyed. Aspiration lesion of the medial septal area (MS) including the vertical limb of the diagonal band nucleus (DBN) caused increased latency to the onset of convulsions, whereas damage to the nucleus basalis magnocellularis (NBM), nucleus accumbens, or both MS and NBM did not cause anticonvulsant effects. Saporin lesion of MS, DBN (horizontal limb), or MS + DBN had no anticonvulsant effects, suggesting that aspiration lesion of MS disrupted pathways beyond cholinergic ones. Severe aphagia/adipsia and reduced body weight occurred in rats with lesions in the septal area. In separate sham operated rats, a strong positive correlation was found between body weight and latency to onset of convulsions in response to soman. Thus, weight loss and a relatively high dose of soman (1.6 × LD 50) in this context may have masked potential anticonvulsant effects among some lesioned animals. It is inferred that MS and AT/piriform cortex occur as prime target areas for induction of seizures by soman.

The Effects of Ascorbic Acid on Penicillin‐induced Epileptiform Activity in Rats

Epileptic seizure results from excessive discharge in a population of hyperexcitable neurons. A number of studies help to document the effects of active oxygen free radical scavengers such as alpha-tocopherol or ascorbic acid (vitamin C). In the present study, we examined the effects of ascorbic acid, at the six different doses, on penicillin-induced epileptiform activity. A single microinjection of penicillin (2.5 microl, 500 units, intracortically) into the left sensorimotor cortex induced epileptiform activity within 2-5 min, progressing to full seizure activity lasting approximately 3-5 h. In the first set of experiments, 30 min after penicillin injection, six different doses of ascorbic acid (25, 50, 100, 200, 400, or 800 mg/kg) were administered intraperitoneally (IP). The other group of animals received the effective dose of ascorbic acid (100 mg/kg, IP) for 7 days. Ascorbic acid administration was stopped 24 h before penicillin treatment. Another group of rats received the effective dose of ascorbic acid (100 mg/kg, IP) 30 min before penicillin treatment. In the second set of experiments, the lipid peroxidation (MDA) and reduced glutathione (GSH) levels of brain were measured in the control, control + ascorbic acid, penicillin, and penicillin + ascorbic acid groups. Ascorbic acid, at the low dose (50, 100 mg/kg, 30 min after penicillin injection), decreased both the frequency and amplitude of penicillin-induced epileptiform activity in rats. Ascorbic acid, at intermediate doses (200, 400 mg/kg, 30 min after penicillin injection), decreased the frequency of epileptiform activity without changing the amplitude. Ascorbic acid, at the lowest dose (25 mg/kg) and highest dose (800 mg/kg) (30 min after penicillin injection), did not change either the frequency or amplitude of epileptiform activity. Ascorbic acid, at the low dose (100 mg/kg) was the most effective dose in changing the frequency and amplitude of penicillin-induced epileptiform activity. Pretreatment with ascorbic acid (100 mg/kg) 30 min before penicillin treatment caused a significant delay in the onset of penicillin-induced epileptiform activity. Pretreatment with ascorbic acid (100 mg/kg) for 7 days did not change the latency of epileptiform activity. The most effective dose of ascorbic acid (100 mg/kg) prevented both the decrease in GSH level and the increase in lipid peroxidation level (MDA) occurring after penicillin-induced epileptiform activity. These data indicate that ascorbic acid has neuroprotective activity against penicillin-induced epileptiform electrocorticogram activity.

The influence of ethanol intake and its withdrawal on the anticonvulsant effect of α-tocopherol in the penicillin-induced epileptiform activity in rats

Previous studies proposed the existence of a relationship between epilepsy and ethanol. Ethanol may have either proconvulsive or anticonvulsive effects on epileptic activity in different experimental epilepsy models. The influence of high dose ethanol intake and its withdrawal on the anticonvulsant effect of α-tocopherol was examined after intracortical injection of penicillin (500 units) to induce epileptiform activity. Thirty minutes after penicillin injection, the most effective dose of α-tocopherol (500 mg/kg) was administrated intramuscularly (i.m.). Ethanol-treated rats received a daily dose of 9.0 g/kg of 30% ethanol solution via an oesophageal probe for 15 days. All rats in the withdrawal group were anesthetized for induction of penicillin-induced epileptiform activity 28 h after the last ethanol administration. The epileptiform activity was verified by electrocorticographic (ECoG) recordings. Ethanol, in a dose of 9 g/kg, significantly decreased the mean frequency of penicillin-induced epileptiform ECoG activity without changing the amplitude. The mean frequency of ECoG activity was decreased in the 60 and 70 min period from penicillin injection in the ethanol-treated + α-tocopherol and ethanol withdrawal + α-tocopherol groups compared with the penicillin-injected (500 units, i.c.) group, respectively. α-Tocopherol was more effective in decreasing the mean frequency of epileptiform activity in the ethanol + α-tocopherol group than in other α-tocopherol administrated groups. Ethanol withdrawal caused an increase in frequency of epileptiform activity in the withdrawal + α-tocopherol group compared with other α-tocopherol administrated groups. α-Tocopherol did not affect the amplitude of epileptiform activity in any group. Possible mechanisms of ethanol influence on the neuroprotective actions of α-tocopherol are still a crucial issue associated with epilepsy.

Anticonvulsant effects of focal and intracerebroventricular adenosine on penicillin-induced epileptiform activity in rats

Adenosine has potent anticonvulsant effects on various models of experimental epilepsy. In the present study, we examined the effects of focal and intracerebroventricular (i.c.v.) adenosine on penicillin-induced epileptiform activity in Wistar rats. The effects of theophylline, a non-selective adenosine receptor antagonist, were also researched. The recordings of electrocorticogram (ECoG) were carried out by using a data acquisition system, under urethane anesthesia. Adenosine was given in doses of 1, 10 and 100 μg/rat via focal and i.c.v. 30 min after penicillin administration. Theophylline was injected in doses of 1, 10 and 100 μg/rat by i.c.v. too. Adenosine administration significantly decreased the spike frequency while theophylline increased. Focal adenosine is more effective than i.c.v. adenosine. 100 μg adenosine is an effective dose that causes a decrease in epileptiform activity during experiments. We also demonstrated that 100 μg theophylline significantly increased epileptiform activity. Our findings suggest that focal adenosine is more effective than i.c.v. adenosine on epileptiform activity.

The involvement of nitric oxide in the anticonvulsant effects of α-tocopherol on penicillin-induced epileptiform activity in rats

A variety of animal seizure models exist which help to document the effects of alpha-tocopherol (Vitamin E) and specify its action. In the present study, we provide further evidence for the functional involvement of NO in the anticonvulsant effects of alpha-tocopherol on penicillin-induced epileptiform electrocorticographical (ECoG) activity in rats. The epileptiform ECoG activity was induced by microinjection of penicillin into the left sensorimotor cortex. Thirty minutes after penicillin injection, the most effective dose of alpha-tocopherol (500 mg/kg) was administrated intramuscularly (i.m.). Alpha-tocopherol decreased the frequency of penicillin-induced epileptiform ECoG activity without changing the amplitude. The effect of systemic administration of nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) and NO substrates, L-arginine and sodium nitro prusside (SNP) on anticonvulsive effects of alpha-tocopherol was investigated. The administration of L-NAME (60 mg/kg, i.p.) did not influence the frequency of epileptiform ECoG activity while administration of L-arginine (500 mg/kg, i.p.) and SNP (6 mg/kg, i.p.) significantly decreased in the penicillin-treated group. The administration of L-NAME (60 mg/kg, i.p.) 10 min after alpha-tocopherol (500 mg/kg, i.m.) application reversed the anticonvulsant effects of alpha-tocopherol. The administration of L-arginine (500 mg/kg, i.p.) and SNP (6 mg/kg, i.p.) did not affect the frequency of epileptiform ECoG activity in alpha-tocopherol supplemented group. L-arginine and SNP did not provide an additional anticonvulsant effect in alpha-tocopherol supplemented group. These results support the involvement of the nitric oxide pathway in the anticonvulsant effect of alpha-tocopherol on the penicillin-induced epileptiform ECoG activity.

The effects of ethanol intake and withdrawal on penicillin-induced epileptiform activity in rats

Previous experiments have shown that ethanol may have either pro-convulsive or anti-convulsive effects on epileptic activity in different experimental epilepsy models. In this study, the effect of low dose ethanol and its withdrawal on penicillin-induced epileptiform activity in rat was investigated. Eight groups of adult, male Wistar rats were studied: (1) control, (2) penicillin pretreated (500 units), (3) α-tocopherol (500 mg/kg, i.m.), (4) penicillin pretreated + α-tocopherol, (5) ethanol-treated (3 g/kg, per day, for 15 days, intragastrically) + penicillin, (6) ethanol-treated + penicillin + α-tocopherol, (7) ethanol withdrawal + penicillin, (8) ethanol withdrawal + penicillin + α-tocopherol. Each animal group was composed of seven rats. The epileptiform activity was verified by electrocorticographic (ECoG) recordings. The epileptiform activity was induced by microinjection of penicillin into the left sensorimotor cortex. Administration of ethanol (3 g/kg, per day, for 15 days, intragastrically) did not change either frequency or amplitude of penicillin-induced epileptiform activity. The frequency and amplitude of epileptiform activity were evaluated 40 h after the last ethanol administration in withdrawal groups. There was no significant change in the mean frequency and amplitude of epileptiform activity compared with penicillin pretreated and ethanol-treated groups. The effective dose of α-tocopherol (500 mg/kg, i.m.) significantly decreased the mean frequency of epileptiform activity in the 60, 70, and 120 min after α-tocopherol injection in penicillin pretreated, ethanol-treated, ethanol withdrawal groups, respectively. However, α-tocopherol did not affect the amplitude of epileptiform activity in all groups. In conclusion, the present results indicate that low dose of ethanol does not have either anticonvulsive or proconvulsive effect on penicillin-induced epileptiform activity. α-Tocopherol has anti-convulsive effect on penicillin-induced epileptiform activity in effective dose.

The effects of octanol on penicillin induced epileptiform activity in rats: An in vivo study

The common features of all types of epilepsy are the synchronized and uncontrolled discharges of nerve cell assemblies. The reason for the pathologically synchronized discharges of the neuron is not exactly known yet. Recent reports claim that gap junctions have a critical role in neuronal synchronization. The present study was planned to investigate the effects of octanol, a gap junction blocker, on penicillin-induced experimental epilepsy. Permanent screw electrodes allowing EEG monitoring from conscious animals and permanent cannula providing the administration of the substances to the brain ventricle were placed into the cranium of rats under general anesthesia. After the postoperative recovery period, epileptiform activity was generated by injecting 300 IU crystallized penicillin through the ventricular cannula. When epileptiform activity, monitored from a digital recording system, reached at its maximum intensity, octanol was applied in the same way as penicillin administered. Application of octanol caused an inhibition in the epileptiform activity. Vehicle solution alone did not affect the epileptiform activity. Results of this study suggest that the blockade of electrical synapses may contribute to the prevention and amelioration of epileptic activity. Production of gap junction blockers selective for connexin types is needed. Further studies on the differential roles of gap junctions on certain epileptiform activities are required.

Anticonvulsant effects of melatonin on penicillin-induced epileptiform activity in rats

In the present study, we investigated the effects of melatonin on penicillin-induced epileptiform activity in female Wistar rats. The left cerebral cortex was exposed by craniotomy under urethane anesthesia for the induction of epilepsy by intracortical microinjection of penicillin (200 IU) into the left sensorimotor cortex. The epileptiform activity was analyzed by electrocorticogram (ECoG). Ten minutes before the penicillin injection, 20, 40 or 80 μg of melatonin was administered intracerebroventricularly and ECoG was monitored for 1 h. Forty or 80 μg of melatonin significantly increased the latency to epileptiform activity. Furthermore, melatonin significantly decreased the frequency of spike and spike-wave activity, whereas the amplitude of spikes remained unchanged. In conclusion, data obtained from the present study suggest that melatonin suppresses penicillin-induced epileptiform activity, and it may be an endogenous anticonvulsant.

The effects of vitamin E on penicillin-induced epileptiform activity in rats

Epilepsy is a disorder characterized by recurrent seizures, which can increase the content of reactive oxygen in the brain. Active oxygen free radical scavengers such as ascorbic acid or alpha-tocopherol (vitamin E) might prevent epilepsy. A variety of animal seizure models exist which help to document the effects of vitamin E and specify its action. In this study, we have evaluated dose-dependent effect of alpha-tocopherol on penicillin-induced epileptiform activity, analyzed by electrocorticogram (ECoG). The epileptiform activity was induced by microinjection of penicillin into the left sensorimotor cortex. Thirty minutes after penicillin injection, 100, 300, or 500 mg/kg of alpha-tocopherol was administrated intramuscularly (i.m.). alpha-Tocopherol (100, 300, or 500 mg/kg) alone did not significantly change the spike amplitudes in non-penicillin pretreated control animals. alpha-Tocopherol of 300, or 500 mg/kg significantly decreased the frequency of epileptiform activity in the penicillin-pretreated animals. The low dose of alpha-tocopherol (100 mg/kg) did not significantly change either amplitude or frequency of epileptiform activity. alpha-Tocopherol of 500 mg/kg i.m. was the most effective dose in changing of frequency on penicillin-induced epileptiform activity. The anti-convulsant effects of alpha-tocopherol appeared 80, 60, 30 min after alpha-tocopherol injection in 300, 500, and 3 day vitamin E supplemented groups. These data indicate that alpha-tocopherol decreases the frequency of penicillin-induced epileptic activity.

The effect of leptin on penicillin-induced epileptiform activity in rats

Leptin is an adipose tissue-derived peptide hormone, which acts as a satiety factor to reduce appetite by interactions with hypothalamic neurons. The other possible physiological functions of leptin are still unclear. In this study, we have evaluated dose-dependent effect of leptin on penicillin-induced epileptiform activity, analyzed by electrocorticogram (ECoG). The epileptiform activity was induced by microinjection of penicillin into the left sensorymotor cortex. Thirty minutes after penicillin injection, 1, 2 or 10 μg of leptin was administrated intracerebroventricularly (i.c.v .). Leptin (1, 2 or 10 μg) alone did not significantly change the spike amplitudes in non-penicillin pretreated control animals. One or two micrograms of leptin significantly increased the frequency of epileptiform activity in the penicillin-pretreated animals. The high dose of leptin (10 μg) did not significantly change either amplitude or frequency of epileptiform activity. One microgram i.c.v. leptin was the most effective dose in changing of frequency on penicillin-induced epileptiform activity. The proconvulsant effects of leptin appeared 90 min after leptin (1 and 2 μg) injection. These data indicate that leptin increases the frequency of penicillin-induced epileptic activity. We speculate that this action of leptin might suggest that leptin may be a proconvulsant substance.