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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in synaptic potentials during each train stimulation (tetanic responses) have been suggested to intimately relate to the development of kindling. We examined the effects of an NMDA antagonist, carboxypiperazinephosphonate (CPP), and a GABAergic antagonist, picrotoxin, on entorhinal tetanic responses evoked by train stimuli (10 Hz, 100 pulses) at the developmental stage (seizure stage; 0-2) of amygdala kindling in conscious rats, to clarify the significance of facilitation in tetanic responses and the roles of NMDA and GABA receptors in the development of kindling. Facilitation of tetanic responses was noted as a progressive increase in both amplitude and duration of negative potentials in the tetanic responses, especially during the later half of train pulses (51-100). The negative potential area (mV x ms) of the averaged tetanic responses was used as an estimate of the magnitudes of excitatory synaptic activity in the tetanic responses, and correlated significantly (P < 0.001) with the duration of afterdischarges (AD). CPP (10 mg/kg) reversibly blocked AD in association with a significant decrease (P < 0.05) in the negative potential area. The CPP-sensitive component consisted of a slow negative potential with a duration longer than 60 ms and was greater in the later tetanic responses (51-100) than the earlier ones (1-50). Picrotoxin (2-3 mg/kg), which did not produce convulsions, significantly (P < 0.005) increased the negative potential area in the tetanic responses in association with a reversible decrease in the AD threshold. Although positive potentials ascribable to inhibitory synaptic activity were often negligible in the tetanic responses in controls, picrotoxin further decreased the positive potentials of tetanic responses, if any.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of an N-methyl-D-aspartate antagonist and a GABAergic antagonist on entorhinal tetanic responses during the early stages of amygdala kindling in rats. 809 Mar 69

There are two phases to the behavioral response to injection of formalin. After an initial vigorous response, a period of reduced pain occurs 10 to 15 min after formalin, followed by reemergence of pain-related behaviors. These phases are believed to represent acute chemical stimulation of afferent neurons followed by injury-related inflammatory pain. Pentobarbital (10, 15, or 25 mg/kg), diazepam (0.5, 1.5, or 5.0 mg/kg), or ethanol (0.5, 1.0, or 1.5 g/kg) attenuated the diminution of pain between the two phases, so that pain was continuous throughout 60 min of testing, but had no effect on pain scores during the peaks of either phase. The effects of pentobarbital and diazepam were blocked by picrotoxin (2.5 mg/kg), which itself had no effect. Ro 15-1788 also blocked the effect of diazepam. Picrotoxin did not effectively antagonize the effect of ethanol. A high dose of picrotoxin (5.0 mg/kg) caused seizures in some rats and also eliminated the interphase depression of pain. The results suggest that the biphasic time course of formalin pain is produced by a central antinociceptive mechanism that is inhibited by GABAA receptors.
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PMID:Pentobarbital, diazepam, and ethanol abolish the interphase diminution of pain in the formalin test: evidence for pain modulation by GABAA receptors. 827 43

The action of ethosuximide (125 or 250 mg/kg, IP) against picrotoxin-induced seizures (3-6 mg/kg, IP) was assessed in rats 12, 18, 25, and 90 days old. In 18-day-old and older controls, picrotoxin regularly elicited clonic seizures; tonic-clonic seizures were induced in all age categories with high consequent mortality. Only the higher dose of ethosuximide (250 mg/kg) increased the latency of clonic seizures in 18- and 25-day-old pups. Tonic-clonic seizures were delayed by ethosuximide in 12-, 18-, and 90-day-old rats. Picrotoxin-induced lethality was suppressed only in 18- and 90-day-old rats by the 250-mg/kg dose of ethosuximide. In contrast, ethosuximide pretreatment increased the incidence of clonic seizures in 12-day-old rats. The results suggest that only high doses of ethosuximide can suppress clonic seizures, and this action is not consistent. Tonic-clonic seizures probably have model-specific sensitivity to ethosuximide because in previous studies ethosuximide completely suppressed pentylenetetrazol-induced tonic-clonic seizures but had no effect on kainic acid-induced tonic-clonic seizures. The suppression of mortality rates is probably due to nonspecific effects of high doses of ethosuximide.
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PMID:Ethosuximide suppresses seizures and lethality induced by picrotoxin in developing rats. 846 8

Picrotoxin administration decreased the incorporation of labelled phosphate in neurospecific protein synapsin I in vitro in cortex. In the animal hippocampus, the incorporation was more expressed. The data obtained suggest that activation of the cAMP-dependent phosphorylation occurs during seizure in the cortex.
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PMID:[The effect of picrotoxin-induced seizure activity on the cAMP-dependent phosphorylation of synapsin-I in rats]. 905 91

Picrotoxin, an antagonist of GABA(A) receptor-mediated activity, elicited 320- to 475-ms synchronized bursts from the CA3 region of the guinea pig hippocampal slice. The addition of the selective group I metabotropic glutamate receptor (mGluR) agonist (S)-3, 5-dihydroxyphenylglycine (DHPG, 50 microM; 20- to 45-min application) gradually increased the burst duration to 1-4 s; this effect persisted 2-3 h after agonist removal. To determine whether the induction of this long-lasting effect required ongoing synchronized activity during mGluR activation, DHPG application in a second set of experiments took place in the presence of CNQX and (R, S)-CPP, antagonists of AMPA/kainate and NMDA receptors, respectively. In these experiments, synchronized bursting was silenced during the mGluR agonist application, yet after wash out of the DHPG and the ionotropic glutamate receptor (iGluR) blockers, epileptiform discharges 1-10 s in duration appeared and persisted at least 2 h after wash out of the mGluR agonist. The potentiated bursts were reversibly shortened by application of 500-1,000 microM (+)-alpha-methyl-4-carboxyphenylglycine (MCPG) or (S)-4-carboxyphenylglycine (4CPG), agents with group I mGluR antagonist activity. These data suggest that transient activation of group I mGluRs, even during silencing of synchronized epileptiform activity, may have an epileptogenic effect, converting brief interictal-length discharges into persistent seizure-length events. The induction process is iGluR independent, and the maintenance is largely mediated by the action of endogenous glutamate on group I mGluRs, suggesting that autopotentiation of the group I mGluR-mediated response may underlie the epileptogenesis seen here.
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PMID:Group I mGluR-mediated silent induction of long-lasting epileptiform discharges. 1044 1

The effects of allopregnanolone and midazolam, given intracerebroventricularly, on the behavioral and biochemical effects of picrotoxin, were examined in a model of neurotoxin-induced seizures, in mice. After acute injections, midazolam (ED(50)=39.8 nmol) and allopregnanolone (ED(50)=11.0 nmol) produced similar and dose-dependent protection against picrotoxin-induced seizures. Picrotoxin given intraperitoneally at the ED(85) dose decreased significantly the concentration of serotonin (5-HT), dopamine (DA), homovanilic acid (HVA) and 3,4-dihydroxyindolacetic acid (DOPAC), in the mouse striatum and the frontal cortex, in the period of time immediately preceding the onset of seizures. A single injection of allopregnanolone more potently, in comparison to midazolam, antagonized the biochemical action of picrotoxin, abolishing its effects on DA, HVA and 5-HT concentration, in the mouse striatum and the frontal cortex. These results for the first time provide a direct argument for an involvement of central dopaminergic and serotonergic systems in the seizure development. The present data add also to the accumulating evidence suggesting a favorable pharmacological profile for some neurosteroids currently considered to have a future role in the management of epilepsy.
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PMID:Antagonism of picrotoxin-induced changes in dopamine and serotonin metabolism by allopregnanolone and midazolam. 1206 90

Ivermectin, a mixture of 22,23-dihydroavermectin B1a (> or = 80%) and B1b (< or =20%), is produced by Streptomyces avermectilis, an actinomycete. It is a macrocyclic lactone disaccharide, a member of the avermectin family, and is used as an antiparasitic drug. Previous studies performed in our laboratory showed that doramectin, another avermectin drug, interferes with GABAergic-related behaviours, leading to anxiety and seizures. The objective of the present study was to examine the effects of ivermectin (0.5 and 1.0 mg/kg) on the central nervous system of rats, using behavioural models related to GABAergic neurotransmission. A known anxiolytic drug, diazepam, was used as a positive control. Open field and elevated plus-maze behaviours, as well as conflict behaviour to a conditioned response, were assessed. The effects of ivermectin and diazepam in reversing the anxiety induced by picrotoxin was studied. The protective effects of ivermectin on pentylenetetrazole- and picrotoxin-induced seizures were also investigated. In the open field, 1.0 mg/kg ivermectin decreased locomotion frequency at 15 and 60 min of observation, rearing behaviour showed a biphasic effect at 15 and 30 min and duration of immobility was increased in all sessions after 1.0 mg/kg ivermectin. These data suggest anxiolytic or sedative effects. Ivermectin and diazepam both had a tendency to cause an increase both in the number of entries into the open arms and on the time spent in the open arms of an elevated plus-maze. Picrotoxin on its own reduced the number of entries as well as the time spent in the open arms. Both diazepam and ivermectin reversed these effects of picrotoxin. In conflict behaviour analysis, ivermectin and diazepam gave the classic effect of an anxiolytic drug, reversing the conditioned response to shock. Ivermectin protected rats from the convulsant effects of pentylenetetrazole but not from those of picrotoxin. Thus, ivermectin had the pharmacological profile of an anxiolytic drug with GABAergic properties. The lack of effect on seizures induced by picrotoxin suggests that the action of ivermectin is different from that of the benzodiazepine drugs.
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PMID:Possible anxiolytic effects of ivermectin in rats. 1218 2

The aim of this study was to examine the response of phrenic and hypoglossal motor outputs to hyperoxia and 11% hypoxia during picrotoxin-induced seizures. Adult rats were anesthetized with a mixture of urethane with alpha-chloralose. The animals were bilaterally vagotomized, paralyzed, and artificially ventilated. Picrotoxin was administered intravenously in a cumulative dose until seizures occurred. The response to changes in oxygen tension was studied after the convulsive dose of picrotoxin and compared with the baseline level. The results show that the picrotoxin-induced seizures evoked a complex respiratory response that consisted of an augmentation of phrenic and hypoglossal nerve activities and irregular disturbances in phasic respiratory discharges. The excitation of the hypoglossal activity appeared earlier and showed a more irregular pattern than that of the phrenic activity. Hyperoxia elicited a similar decrease in neural respiratory outputs during the control and seizure conditions, suggesting the unaltered peripheral chemoreceptor mechanism. In the pre-seizure condition, hypoxia caused an initial excitation of the phrenic and hypoglossal outputs followed by some decline of the effect. During seizures, the striking effect of hypoxia was a decrease of the respiratory rate. A biphasic response to hypoxia was maintained in the hypoglossal activity due to stimulation of the hypoglossal amplitude. In contrast, in the phrenic activity the excitatory phase of hypoxia was absent and depression ensued. The mechanism underlying the facilitation of hypoxic respiratory depression during seizures is discussed.
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PMID:Hypoglossal and phrenic nerve responses to changes in oxygen tension during picrotoxin-induced seizures in the rat. 1561 91

Epilepsy is an important neurological disorder in dogs. Belladonna 200C was evaluated in 10 dogs with idiopathic epilepsy. During the seizure phase, 3-4 drops of Belladonna 200C were administered orally at 15 min intervals until considerable reduction in seizure activity, then four times daily. Four dogs with head shaking syndrome in addition to seizures were given Cocculus 6C, 3-4 drops orally weekly for 3 months in addition. Numbers of fits reduced to 2-3 during first 2 weeks post-therapy and then became occasional in next 2 weeks. With continuation of Belladonna therapy, no fits were observed during 2-7 months follow-up. In two cases epileptic fits reappeared within 15-25 days of cessation of therapy. Belladonna therapy was resumed and seizure control was again achieved. Owners were advised to continue the therapy at least twice daily until there were no fits for 2-3 months. Liver specific enzymes were monitored, no abnormalities were observed.
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PMID:Clinical management of idiopathic epilepsy in dogs with homeopathic Belladonna 200C: a case series. 1722 48

Extracellular ion concentrations change during seizures in seizure models. [K(+)](o) increases and [Ca(2+)](o) decreases, resulting from population discharges, enhanced neuronal excitability, though not obviously before seizure onset. In acute pharmacological epilepsy models, there are striking increases in preictal high-frequency (gamma) electroencephalographic (EEG) activity. It is not known whether enhanced gamma EEG results in ionic changes, because gamma and ions have not been measured simultaneously. In this study, unanesthetized, paralyzed rats were given intravenous injections of kainic acid or picrotoxin to induce EEG discharges. Changes in EEG, [K(+)](o), and [Ca(2+)](o) in cortex and hippocampus were recorded. Kainic acid caused small [K(+)](o) fluctuations, without a temporal relationship of these with increased gamma EEG or with onset of discharges. Gamma EEG increases after picrotoxin also failed to affect [K(+)](o) and [Ca(2+)](o). Picrotoxin-induced electrical discharges led to [K(+)](o) rises of >9 mM and [Ca(2+)](o) falls of 0.1-0.2 mM. Kainic acid-induced discharges generated only moderate (2-3 mM) rises in [K(+)](o) and no changes in [Ca(2+)](o). In both models, there were large potassium rises (15-80 mM) and calcium falls (>0.5 mM), suggesting spreading depressions. Small [K(+)](o) fluctuations after kainic acid are consistent with disruption in potassium homeostasis, possibly because of depolarization of astrocytes. To reveal possible latent [K(+)](o) or [Ca(2+)](o) changes, we injected fluorocitrate intracortically to impair astrocytic function, before administering picrotoxin. Even fluorocitrate did not cause gamma-related ion changes but did cause low-magnitude, transient, potassium increases and slower potassium homeostasis during discharges, minor changes consistent with involvement of both astrocytes and neurons in [K(+)](o) regulation. (c) 2007 Wiley-Liss, Inc.
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PMID:Preseizure increased gamma electroencephalographic activity has no effect on extracellular potassium or calcium. 1724 72


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