Anticonvulsant activity of Caryocar coriaceum Wittm. fixed pulp oil against pentylenetetrazol-induced seizures

Objectives: Epilepsy is a common brain disease and a major worldwide public health problem. The seizures in a significant number of patients suffering from epilepsy remain inadequately controlled by currently available pharmacological treatments. Accordingly, there is a need for the discovery of new anticonvulsant approaches with improved efficacy and a better safety profile. In this context, natural products can be a valuable source of substances with potential anticonvulsant activity. In the present study, we tested the anticonvulsant potential of Caryocar coriaceum Wittm., a plant native from the Brazilian Cerrado biome (tropical savanna ecoregion).

Methods: Adult male C57BL/6 mice were treated with increasing doses of the fixed oil obtained from the pulp of Caryocar coriaceum Wittm. Seizure activity was induced by PTZ (60 mg/kg, i.p.), and evaluated by behavioral and electrographic methods. Potential adverse effects were investigated in the open-field, rotarod, forced swim, or object recognition tests. The antioxidant potential of the oil was evaluated by the DPPH scavenging assay.

Results: Administration of the oil at the dose of 100 mg/kg increased the latency for the first myoclonic jerk and the first generalized tonic–clonic seizures. The duration of generalized convulsions induced by PTZ was not altered. No significant behavioral adverse effects were detected in the open-field, rotarod, forced swim, or object recognition tests. Interestingly, a significant antioxidant activity of Caryocar coriaceum Wittm. fixed pulp oil was detected in the DPPH scavenging assay.

Discussion: Natural products can be a valuable source of substances with potential anticonvulsant activity and improved safety profile. Further studies are needed to evaluate the mechanisms underlying the anticonvulsant effects of Caryocar coriaceum Wittm. fixed pulp oil as well as the potential of the oil as a source of new anticonvulsant compounds.     

Imaging the neural substrates involved in the genesis of pentylenetetrazol-induced seizures

PURPOSE: Functional imaging of animal models makes it possible to map the functional neuroanatomy contributing to the genesis of seizures. Pentylenetetrazol (PTZ)-induced seizure in rats, a relevant model of human absence and of generalized tonic-clonic epilepsy, was used to stimulate seizure activity within 30 s of administration while collecting continuous, high-resolution, multislice images at subsecond intervals. METHODS: Pilot studies were conducted to establish a quick and effective PTZ model for the imaging experiments. PTZ was then used to stimulate seizure activity in rats while collecting multislice functional MRI (fMRI) images from the entire forebrain at 4.7 Tesla. Ethosuximide (ESM) also was used to block seizure activity. RESULTS: Within 2-4 s of PTZ administration, a rapid increase in blood oxygen level-dependent (BOLD) signal intensity was noted in the thalamus, especially the anterior thalamic nuclei. Activity in the anterior thalamus peaked approximately 15 s before seizure onset and was more than twofold greater than that in all other thalamic areas. The retrosplenial cortex showed a twofold greater increase in activity as compared with other cortical areas, also peaking at approximately 15 s. The dentate gyrus was twice as active as other hippocampal areas but peaked just before seizure onset. Treatment with ESM blocked seizures, decreasing PTZ-induced activation in most forebrain areas. The anterior thalamus and retrosplenial cortex were essentially blocked by pretreatment with ESM. CONCLUSIONS: The anterior thalamus, retrosplenial cortex, and dentate gyrus show the greatest increases in BOLD signal activity before seizure onset. Neurons in these areas may contribute to the neural network controlling the initiation of generalized tonic-clonic seizure.     

Effects of carbamazepine on bicuculline- and pentylenetetrazol-induced seizures in developing rats.

The anticonvulsant effect of carbamazepine (CBZ) was examined in 10-, 18- and 25-day-old Wistar albino rats into which bicuculline or pentylenetetrazol had been systemically injected to induce generalized epileptic manifestations typical for the specific age of the animals. The results showed that: a) in developing rats, CBZ appears to be more effective in the pentylenetetrazol than the bicuculline model of epilepsy; b) in both models of epilepsy the efficacy of CBZ increases with the age of the animals; and c) among the various epileptic manifestations, the tonic phase is the most sensitive to the anticonvulsant effect of CBZ. These conclusions are correlated with the different levels of cerebral maturation of the animals, and are discussed with reference to the mechanisms of action of CBZ and bicuculline or pentylenetetrazol.     

Inhibitor effect of dexketoprofen in rat model of pentylenetetrazol-induced seizures

Objectives: The relationship between epilepsy and inflammation is known, and it has been reported that there is an increase in cyclooxygenase (COX) levels in epilepsy. We aim to reveal the anticonvulsant effects of dexketoprofen in pentylenetetrazol (PTZ)-induced seizures in rats.

Materials and Methods: Forty-eight male Sprague-Dawley rats, 24 of them for EEG recording and 24 of them are for behavioral studies, were randomly divided in two groups: Group A for EEG recordings and Group B for behavioral assessment. A weight of 70 mg/kg PTZ was used for behavioral studies after dexketoprofen administration. Thirty-five milligrams per kilogram PTZ were used for EEG recording after dexketoprofen administration. The electrodes were implanted on dura over the left frontal cortex and the reference electrode was implanted over the cerebellum for EEG recording. The Racine convulsion scale (RCS), first myoclonic jerk (FMJ) onset time, and spike percentages were evaluated between the two groups.

Results: There was a significant (P< 0·05) difference between the RCS, FMJ onset time (P< 0·001), and spike percentage (P< 0·05) between the groups (Group 2 compared with Groups 3 and 4).

Conclusion: Dexketoprofen has an antiepileptic feature and this effect increases as the dosage increases, however it is currently unknown through which mechanism this drug shows its anticonvulsant effect. Dexketoprofen, in the group of NSAIDs, shows an anticonvulsant effect on PTZ-induced epilepsy model. This study suggests that dexketoprofen can preferably be used with NSAIDs for epileptic patients in clinical practice.     

Anticonvulsant effects of dipotassium clorazepate on hippocampal kindled seizures in rats

We examined the anticonvulsant properties of dipotassium clorazepate (DC) against hippocampal kindled seizures in rats. Adult male Wistar rats were subjected to kindling 1 week after the implantation of electrodes. After five stage 5 seizures were induced, the generalized convulsion triggering threshold (GST) was determined. Dipotassium clorazepate was administered intraperitoneally in rats that showed two stable stage 5 seizures induced at the GST current intensity. Dipotassium clorazepate at doses of 1 mg/kg or more produced an anticonvulsant effect, but did not readily suppress limbic seizures. Dipotassium clorazepate did not completely suppress after-discharges (AD) even at the highest dose, which was 5 mg/kg. Moreover, raised stimulus intensity failed to affect its efficacy as an anticonvulsant. The results of the present study suggest that DC has a modest anticonvulsant potency. It is reasonable to assume that its anticonvulsant efficacy is primarily due to attenuation of AD propagation rather than the raising of the seizure triggering threshold at the kindling focus.     

Anticonvulsant,neuroprotective and behavioral effects of organic and conventional yerba mate (Ilex paraguariensis St. Hil.) on pentylenetetrazol-induced seizures in Wistar rats

Epilepsy, which is one of the most common neurological disorders, involves the occurrence of spontaneous and recurrent seizures that alter the performance of the brain and affect several sensory and behavioral functions. Oxidative damage has been associated with post-seizure neuronal injury, thereby increasing an individual's susceptibility to the occurrence of neurodegenerative disorders. The present study investigated the possible anticonvulsive and neuroprotective effects of organic and conventional yerba mate (Ilex paraguariensis), a plant rich in polyphenols, on pentylenetetrazol (PTZ)-induced seizures in Wistar rats. The behavioral and polyphenolic profiles of the yerba mate samples were also evaluated. Infusions of yerba mate (50 mg/kg) or distilled water were given to rats for fifteen days by oral gavage. On the 15th day the animals were subjected to open field test, and exploratory behavior was assessed. Subsequently, 60 mg/kg PTZ (i.p.) was administered, and animals were observed for the appearance of convulsions for 30 min. Latency for the first seizure, tonic–clonic and generalized seizures time, frequency of seizures and mortality induced by PTZ were recorded. The animals were then sacrificed, and the cerebellum, cerebral cortex and hippocampus were quickly removed and frozen to study the neuroprotective effects of yerba mate. The oxidative damage in lipids and proteins, nitric oxide levels, the activities of the antioxidant enzymes superoxide dismutase (Sod) and catalase (Cat) and non-enzymatic cellular defense (sulfhydryl protein) were quantified in all the tissues. The results showed that organic and conventional yerba mate infusions were able to reduce the frequency of seizures when compared to the PTZ group. Besides, organic yerba mate infusion decreases the tonic–clonic seizures time in relation to the PTZ group. It was also shown that organic and conventional yerba mate infusions reduced the oxidative damage in lipids and proteins and nitric oxide levels and prevented the decrease in Sod and Cat activities and sulfhydryl protein content when compared to the PTZ group in all the CNS tissues assayed. Organic and conventional yerba mate commercial samples did not change the behavior (locomotion, exploration or anxiety) of the treated animals. In both organic and conventional infusions, the presence of the polyphenols rutin, chlorogenic acid and their acyl derivatives were detected, which could be associated with the biological effects observed. These data indicate that yerba mate may provide new perspectives for the development of therapeutic approaches with natural compounds in the pharmaceutical area, both to reduce the convulsions’ frequency and to minimize the neuronal damage associated with recurrent seizures.     

Anticonvulsant action of topiramate against motor seizures in developing rats

PURPOSE: To study the anticonvulsant action of topiramate (TPM) in developing rats. METHODS: Motor seizures were elicited by administering pentylenetetrazol (100 mg/kg subcutaneously) in five age groups of Wistar rats (7, 12, 18, 25, and 90 days old). TPM was administered intraperitoneally in doses from 10 to 640 mg/kg 2 hours before pentylenetetrazol. The time course of TPM action was studied in 12- and 25-day-old rats up to 24 hours after the 160-mg/kg dose, and the incidence and pattern of seizures were evaluated. RESULTS: TPM did not influence minimal seizures (clonus of forelimb and head muscles with preserved righting ability). Generalized tonic-clonic seizures, however, were reliably changed at all developmental stages studied. The tonic phase was suppressed so that the majority of animals exhibited generalized clonic seizures (with a loss of righting reflexes). In addition, the incidence of generalized seizures was decreased after the 20-, 40-, and 80-mg/kg doses in the 7-day-old rat pups. The specific suppression of the tonic phase of generalized seizures was observed up to 12 hours in the 12-day-old rat pups. The same result was obtained over 6 hours after TPM administration in the 25-day-old animals, and with longer intervals the incidence of generalized seizures decreased in this age group. CONCLUSIONS: TPM exhibits stable anticonvulsant action against the tonic phase of generalized tonic-clonic seizures throughout development. In addition, it suppresses all phases of generalized seizures in 7-day-old rats. The anticonvulsant action of TPM lasted longer in 25-day-old than in 12-day-old rats. The two actions of TPM might be ascribed to two different mechanisms of action.     

Acute administration of docosahexaenoic acid increases resistance to pentylenetetrazol-induced seizures in rats

ObjectiveDocosahexaenoic acid (DHA), an omega-3 fatty acid, has been reported to raise seizure thresholds. The purpose of the present study was to test the acute anticonvulsant effects of unesterified DHA in rats, using the maximal pentylenetetrazol (PTZ) seizure model, and also to examine DHA incorporation and distribution into blood serum total lipids and brain phospholipids and unesterified fatty acids. Sedation was measured to monitor for the potential toxicity of DHA.MethodsMale Wistar rats received subcutaneous injections of saline, oleic acid (OA), or DHA. An initial pilot study (Experiment 1) established 400 mg/kg as an effective dose of DHA in the maximal PTZ seizure test. A subsequent time–response study, using 400 mg/kg (Experiment 2), established 1 hour as an effective postinjection interval for administering DHA subcutaneously. A final study (Experiment 3) comprised two different groups. The first group (“seizure-tested rats”) received saline, OA, or DHA (400 mg/kg) subcutaneously, and were seizure tested in the maximal PTZ test 1 hour later to confirm the seizure latency measurements at that time. The second group (“assay rats”) received identical subcutaneous injections of saline, OA, or DHA (400 mg/kg). One hour postinjection, however, they were sacrificed for assay rather than being seizure tested. Assays involved the analysis of serum and brain DHA. Sedation was measured in both Experiment 3 groups during the 1-hour period prior to seizure testing or sacrifice.ResultsAs noted above, 400 mg/kg proved to be an effective subcutaneous dose of DHA (Experiment 1), and 1 hour proved to be the most effective injection–test interval (Experiment 2). In Experiment 3, in the seizure-tested animals, subcutaneous administration of 400 mg/kg of DHA significantly increased latency to PTZ seizure onset 1 hour postinjection relative to the saline- and OA-injected controls, which did not differ significantly from each other (P > 0.05). In the assay animals, no significant effects of treatment on blood serum total lipids or on brain phospholipid or unesterified fatty acid profiles (P > 0.05) were observed. There were also no differences in sedation among the three groups (P > 0.05).ConclusionDHA increases resistance to PTZ-induced seizures without altering measures of sedation and, apparently, without changing DHA concentrations in serum or brain.     

Anticonvulsant effect of gentamicin on the seizures induced by kainic acid

Objective: Epilepsy is a chronic neurological disorder affecting approximately 0.5–2% of the population worldwide. Gentamicin (GM) is an aminoglycoside antibiotic used to treat several types of bacterial infections. We investigate whether the administration of GM can reduce seizures in temporal lobe epilepsy (TLE).

Methods: The animal model of temporal lobe epilepsy (TLE) was established by kainic acid (KA) intrahippocampal injection. Behavioral test and Electroencephalography (EEG) recordings were performed to detect the effects of GM on the seizures triggered by KA injection in rats. Furthermore, immunofluorescence was used to investigate the influence of GM on the c-fos expression in the hippocampus.

Results: Here we found that the intracerebroventricular administration of GM is able to prevent the seizures induced by intrahippocampal kainic acid (KA) injection. Behaviorally, the latent period to the first seizure was significantly prolonged by GM. GM can totally abolish the occurrence of stage IV or V seizures and prominently reduce the total seizure duration. Electrographic recording showed that the latent period to the first seizure, the number and duration of high-amplitude, high-frequency discharges were remarkably reduced by GM. Additionally, the expression of c-fos was significantly decreased in the ipsilateral hippocampus of KA-injected rats treated with GM compared with KA-injected rats treated with saline.

Conclusion: These findings could promote the understanding of the pharmacological effects of GM, enriching the application of gentamicin in clinical practice.     

Antiepileptic effects of inhibitors of nitric oxide synthase examined in pentylenetetrazol-induced seizures in rats

The effects of intraperitoneal and methyl ester, specific inhibitors of nitric oxide (NO) synthase, were examined on the pentylenetetrazol (PTZ)-induced seizures in rats. The incidence and latency for the onset of myoclonic jerks, clonic seizures, and tonic generalized extension were observed as specific parameters among PTZ-induced seizures. Both drugs preferentially suppressed the tonic generalized extension and prolonged the latency for the onset of each parameter, suggesting NO has a significant effect on the PTZ-induced seizure.     

Anticonvulsant effect of intracortical, chronic infusion of GABA in kindled rats: focal seizures upon withdrawal

The behavioral and electrographic effects of chronic (7 days), localized infusion of GABA (100 micrograms/microliter) into the somatomotor cortex of fully amygdala-kindled rats is reported. The animals were stimulated once daily until a stage 5 (generalized clonic seizure) was obtained for five consecutive days. After determination of a stable seizure triggering threshold, the rats were implanted with osmotic minipumps (1 microliter/h for 7 days) connected to previously implanted bilateral cannulae. Amygdala stimulation was continued for 14 successive days. GABA infusion reduced the motor seizure without significantly modifying the limbic afterdischarge. This effect lasted until termination of drug application, with recovery of stage 5 convulsions on the following 3 to 5 days. No effects were observed in saline-infused animals or in rats with unilateral GABA treatment. Upon cessation of GABA treatment (removal of the osmotic devices by day 7 postimplantation), spontaneous epileptic discharges localized to the infusion sites appeared. In some animals, the abnormal activity was accompanied by behavioral signs of myoclonus. This cortical hyperexcitability lasted 2 to 24 h, with complete recovery afterward. These data indicate that two types of focal epilepsy may coexist independently in the same animal and provide confirmation of previous observations in the monkey on the existence of a "GABA-withdrawal syndrome" after chronic, focal infusion of the amino acid.     

Effect of minocycline on pentylenetetrazol-induced chemical kindled seizures in mice

Inflammation is one of the mechanisms involved in seizure induction. In this study, the effect of minocycline, an anti-inflammatory drug, was investigated on kindling acquisition. Chemical kindling was induced by injection of a subthreshold dose of pentylenetetrazol (PTZ; 37.5 mg/kg) in mice on every other day. Two groups of animals received minocycline (25 mg/kg) at 1 h before or 1 h after PTZ injection. Following the last PTZ injection, the changes in gene expression of TNF-α receptor, γ₂ subunit of GABA_A receptor and NR₂A subunit of NMDA receptor were assessed in the hippocampus and piriform cortex. Injection of minocycline before PTZ increased the latency to stage 4 seizure, and decreased the duration of stages 4 and 5 seizure. It also prevented the increase in the mRNA of NR₂A subunit of NMDA receptor in the hippocampus and removed the PTZ-induced increase in mRNA of γ₂ subunit of GABA_A receptor in piriform cortex of PTZ kindled mice. Minocycline also prevented the increase in TNF-α receptor gene expression in both hippocampus and piriform cortex. Injection of minocycline after PTZ had no significant effect on measured parameters. Therefore, it can be concluded that minocycline may exert an anticonvulsant effect through preventing the increase in GABA_A and NMDA receptor subunits. These effects are accompanied by a reduction in an important inflammation index, TNF-α receptor.     

Behavioral characterization of pentylenetetrazol-induced seizures in the marmoset

This study was designed to characterize seizures induced with pentylenetetrazol (PTZ) in marmosets. Thirteen adult marmosets (Callithrix sp.) received 20, 30, or 40 mg/kg of PTZ intraperitoneally. PTZ caused all animals to switch their natural behavioral repertoire to early convulsive behavior. Seizure scores were low at lower PTZ doses, whereas the highest dose of PTZ led to seizure scores IV and V (according to Racine's scale) in 69% of animals. To further characterize the model we performed a preliminary evaluation of the efficacy of three antiepileptic drugs: phenobarbital, phenytoin, and carbamazepine. Phenobarbital prevented PTZ-induced seizures in 100% of trials. As expected, phenytoin and carbamazepine were not effective against PTZ-induced seizures. The present study describes the PTZ model of seizures in marmosets with a drug-response profile similar to that of the rodent model, thus bringing to a well-known model (PTZ in rodents) the complexity of a nonhuman primate brain.     

Effect of quinine on electroshock and pentylenetetrazol-induced seizures in mice

1. Effect of quinine on electroshock and pentylenetetrazol (leptazol)-induced seizures was investigated in mice. 2. Quinine (0.1-100 mg/kg, ip) did not protect mice against electroshock seizure. 3. 25-100 mg/kg, ip of quinine reduced the incidence of leptazol (80-90 mg/kg, sc)-induced seizure and significantly prolonged the onset of both myoclonic and tonic phases. 4. d-Amphetamine (2.5 mg/kg, ip), inhibited the protective effect of quinine (100 mg/kg, ip) against leptazol (80-90 mg/kg, sc)-induced seizure and significantly shortened the onset of both myoclonic and tonic phases of the seizure. 5. Pimozide (4 mg/kg, ip) significantly potentiated the protective effect of quinine (50-100 mg/kg, ip) against leptazol (80-90 mg/kg, sc)-induced seizure. 6. These results suggest that quinine in moderate doses, may have slight anticonvulsant properties and that dopaminergic mechanism may be involved in the protective influence of quinine against leptazol-induced seizure in mice.     

Differential effects of atorvastatin treatment and withdrawal on pentylenetetrazol-induced seizures

Purpose: Statins are selective inhibitors of 3‐hydroxyl‐3‐methyl‐glutaryl coenzyme A (HMG‐CoA) reductase, the rate‐limiting enzyme of the mevalonate pathway for cholesterol biosynthesis. Increasing evidence indicates that statins, particularly atorvastatin, are neuroprotective in several conditions, including stroke, cerebral ischemia, traumatic brain injury, and excitotoxic amino acid exposure. However, only a few studies have investigated whether statins modulate seizure activity. In the current study we investigated whether atorvastatin or simvastatin alters the seizures induced by pentylenetetrazol (PTZ), a classical convulsant. Methods: Adult male Wistar rats were treated with atorvastatin or simvastatin for 7 days (10 mg/kg/day). Seizure activity was induced by PTZ (60 mg/kg, i.p.), and evaluated by behavioral and electrographic methods. Cholesterol levels were determined by a standard spectrophotometric method. Blood–brain barrier (BBB) permeability was assessed by the fluorescein method. Atorvastatin levels in the plasma and cerebral cortex were determined by high‐performance liquid chromatography tandem mass spectrometry. Key Findings: We found that oral atorvastatin treatment increased the latency to PTZ‐induced generalized seizures. In contrast, when the 7‐day atorvastatin treatment was withheld for 1 day (i.e., atorvastatin withdrawal), PTZ‐induced seizures were facilitated, as evidenced by a decrease in the latency to clonic and generalized tonic–clonic seizures induced by PTZ. In contrast, simvastatin treatment for 7 days (10 mg/kg/day, p.o.), with or without withdrawal, did not alter PTZ‐induced seizures. Interestingly, the effects of atorvastatin treatment and withdrawal were not accompanied by changes in plasma or cerebral cortex cholesterol levels or in the BBB permeability. Atorvastatin levels in the plasma and cerebral cortex after 7 days of treatment were above the half maximal inhibitory concentration for inhibition of HMG‐CoA reductase, whereas atorvastatin was not detectable in the plasma or cerebral cortex following a 24 h washout period (atorvastatin withdrawal). Significance: We conclude that atorvastatin treatment and withdrawal have differential effects on pentylenetetrazol‐induced seizures, which are not related to changes in plasma or cerebral cortex cholesterol levels or in BBB permeability. Additional studies are necessary to evaluate the molecular mechanisms underlying our findings as well as its clinical implications.     

Anticonvulsant effect of unilateral anterior thalamic high frequency electrical stimulation on amygdala-kindled seizures in rat

Deep brain stimulation (DBS) is an emerging treatment of epilepsy. Anterior nucleus of the thalamus (ANT) is considered to be an attractive target due to its close connection to the limbic structures and wide regions of neocortex. In this study, we examined the effect of unilateral high frequency stimulation (HFS) of the ANT on amygdala-kindled seizures in Wistar rats. When fully-kindled seizures were achieved by daily amygdala kindling, HFS (15 min train of 100 μs pulses at 200 Hz and 450-800 μA) was delivered to the ipsilateral or contralateral ANT immediately before the kindling stimulation for 15 days. HFS of the ipsilateral ANT significantly decreased the incidence of generalized seizures and the mean behavioral seizure stage and afterdischarge duration (ADD), and shortened cumulative ADD and cumulative generalized seizure duration. Furthermore, HFS of the ipsilateral ANT significantly increased the afterdischarge threshold (ADT). Our data suggest that unilateral HFS of the ANT may be an effective method of inhibiting kindled seizures by suppressing the susceptibility to seizures and generating long lasting anti-epileptic effect preventing the recurrence of kindled seizures, providing an alternative to bilateral ANT DBS for refractory epilepsy.     

Anticonvulsant effect of sodium cyclamate and propylparaben on pentylenetetrazol‐induced seizures in zebrafish

Screening for novel anticonvulsant drugs requires appropriate animal seizure models. Zebrafish provide small, accessible, and cost‐efficient preclinical models applicable to high‐throughput small molecule screening. Based on previous results in rodents, we have here examined the effects of artificial sweetener sodium cyclamate and antimicrobial agent sodium propylparaben on a model of pentylenetetrazole (PTZ)‐induced seizures in zebrafish. Sodium cyclamate reduced the bursts of hyperactivity, the spasms, increased the latency to spasms, and the latency to seizure, while propylparaben increased the latency to spasms. The results show the potential of zebrafish to detect novel anticonvulsant compounds while they also demonstrate the ability of two commonly ingested chemical compounds to modify the seizure threshold when were administrated at low concentration.     

Inhibitory effects of powerline-frequency (60-Hz) magnetic fields on pentylenetetrazol-induced seizures and mortality in rats.

The possibility that exposure to powerline frequency (60-Hz) magnetic fields might affect the form or intensity of epileptic seizures, induced by administration of pentylenetetrazol (PTZ) in rats, was examined. Male adult rats were exposed to either 60-Hz magnetic fields with intensities of up to 1.85 gauss (185 microT) or to a sham field condition, for 1 h prior to injections of PTZ (45-75 mg/kg). The subsequent seizures were monitored and recorded on videotape and any subsequent mortalities were noted. Exposure to 60-Hz magnetic fields prior to administration of PTZ was found to significantly (P less than 0.005) reduce the lethality of the drug-induced seizures. The LD50 for the sham-exposed group was 65.88 mg/kg, whereas for the 60-Hz magnetic field-exposed rats, the LD50 was 85.33 mg/kg. In some experiments exposure to the 1.0 and 1.5 gauss magnetic fields also produced significant (P less than 0.05) reductions in seizure durations. These findings suggest that acute exposure to low intensity 60-Hz magnetic fields has an inhibitory effect on the lethality and expression of PTZ-induced seizures in rats. Some possible mechanisms, which could account for these observed effects of magnetic field exposure on seizures, are discussed.