Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The genetically epilepsy-prone (GEP) rat is susceptible to seizure induction by acoustic stimuli. The inferior colliculus (IC) has been implicated as being critically important in audiogenic seizure susceptibility based on lesion, electrical stimulation, and focal implantation experiments. The current study determined that GEP rats were most susceptible to seizure induction by pure tone bursts at 100 dB at a frequency of 12 kHz. IC neurons in the GEP rat exhibited a significantly elevated incidence of a particular response pattern at 12 kHz and at characteristic frequency. This pattern consisted of a peak at the beginning and end of the stimulus (onset-offset response). This response pattern only occurred with high intensity stimuli approximating those which induce seizures and may represent an afterdischarge phenomenon. The response threshold was significantly elevated and tuning characteristics were also significantly altered in IC neurons of GEP rats as compared to normal IC neurons. The latter two findings may be related to the deficit of hearing which is reported in the GEP rat. The increased incidence of onset-offset responses may be due to a decreased efficacy of inhibition in the GEP rat neurons as compared to normal rat neurons.
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PMID:Neuronal response abnormalities in the inferior colliculus of the genetically epilepsy-prone rat. 241 87

The selective non-competitive NMDA receptor antagonist, MK-801, potently blocked convulsions induced in the mouse by N-methyl-DL-aspartic acid (NMDLA) with an i.v. ED50 dose of 0.2 mg/kg. Similar doses of MK-801 were also effective in blocking seizures induced by pentylenetetrazol (PTZ), electroshock and by sound in audiogenic seizure-prone animals. Other less selective non-competitive NMDA receptor antagonists including phencyclidine (PCP), thienylcyclohexylpiperidine (TCP), (+)-N-allylnormetazocine [+)-NANM, (+)-SKF 10,047) and ketamine also blocked NMDLA-induced seizures with a rank order of potency of MK-801 greater than PCP greater than TCP = (+)-NANM greater than ketamine. The competitive NMDA receptor antagonist, 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) blocked NMDLA-induced seizures with an ED50 of 4.5 mg/kg, 22- and 560-fold more potently than the competitive antagonists, 2-DL-amino-7-phosphonoheptanoic acid (2-APH) and 2-DL-amino-5-phosphonovaleric acid (2-APV), respectively. MK-801 was the most potent of the non-competitive antagonists to induce a motor syndrome including head weaving, body rolling, increased locomotion and ataxia, characteristic of the behavioural response to PCP in the mouse. The syndrome was also present following injection of the competitive NMDA receptor antagonists, although they were generally less potent (probably a reflection of poor brain penetration) and less efficacious than the non-competitive antagonists. For all compounds except CPP, the anticonvulsant ED50 dose was close to the minimum effective dose to induce motor stimulation: CPP was 5- to 10-fold more potent as an anticonvulsant.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The behavioural effects of MK-801: a comparison with antagonists acting non-competitively and competitively at the NMDA receptor. 255 Feb 53

1. The participation of telencephalic forebrain structures in the induction of audiogenic seizure (AGS) susceptibility and in the behavioral expression of AGS was investigated in rats. 2. Rats that were initially susceptible (N = 12) or non-susceptible (N = 28) to audiogenic seizure were surgically detelencephalated. 3. A unilateral microinjection of a low dose (30 pmol) of the GABA antagonist bicuculline methiodide (BM) was applied to the inferior colliculus (IC) before the animals were exposed to a 120-dB acoustic stimulus. 4. All susceptible rats still exhibited all components of audiogenic seizure after removal of the telencephalon. 5. After BM microinjection, a higher incidence (66% vs 41%) and shorter latencies (6-20 s vs 9-55 s) of occurrence of tonic seizures were observed in the detelencephalated non-susceptible rats when compared to non-operated non-susceptible rats (N = 12). 6. These results suggest that the induction of the behavioural expression of audiogenic seizures is subserved by brain stem neuronal networks but does not require the telencephalon and that telencephalic structures may exert control over audiogenic seizures by inhibiting IC cells through GABAergic neurons.
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PMID:Increased susceptibility of detelencephalated rats to audiogenic seizures induced by microinjection of bicuculline into the inferior colliculus. 263 27

Wistar-derived male rats were tested for audiogenic seizure (AS) susceptibility, and classified into sensitive (S) and resistant (R) groups. Rats from group R underwent unilateral ablation of the telencephalon, or were detelencephalated (HD), or sham-lesioned, and were tested for audiogenic susceptibility one month and one year after surgery. It was found that previously AS-resistant, HD-operated animals developed generalized tonic-clonic convulsions upon high intensity (110.8 dB) acoustic stimulation, with higher severity and shorter latencies than the susceptible, non-operated control animals. Sham-lesioned R animals maintained their previous resistance to AS. HD-lesioned R animals also presented asymmetric motor patterns, such as gyrating and barrel-rolling behavior, always oriented towards the side contralateral to the lesion. HD-lesioned S animals presented an increase in the severity of seizures, as well as a shortening of the latencies of the running (procursive) and convulsive phases of the seizures. This effect was more marked one year after surgery. Contralateral barrel-rolling behavior was also observed in these animals. The fact that seizure severity increases and latency decreases with time after lesion seems to indicate a role for denervation hypersensitivity and other cerebral plasticity phenomena in explaining the effects of HD lesions on AS. The fundamental neural structures involved appear to be those related to sensorimotor coordinating systems (substantia nigra/pontine-mesencephalic reticular formation and substantia nigra/superior colliculus), the acoustic pathways (inferior colliculus) and their projections to the superior colliculus and reticular formation.
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PMID:Neuroethological evaluation of audiogenic seizures in hemidetelencephalated rats. 273 61

Microinjection of 10 micrograms of either dibutyryl cyclic AMP or 8-bromo-cyclic AMP into the inferior colliculus of normal rats induced audiogenic seizure-like phenomena, which were intensified by sound stimulation. Microinjection of either cyclic AMP derivatives into areas surrounding the inferior colliculus or in the substantia nigra-region did not induce any such effects. These data suggest that there may be a close relationship between audiogenic seizures and cyclic AMP metabolism of the inferior colliculus.
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PMID:Cyclic AMP derivatives injected into the inferior colliculus induce audiogenic seizure-like phenomena in normal rats. 282 67

The purpose of this paper was to study the relationship between different neurotransmitter systems and seizure susceptibility in Mongolian gerbils with genetically determined epilepsy. In these animals, generalized tonic-clonic seizures were induced by stimulation with a blast of compressed air. A variety of drugs that specifically manipulate inhibitory or excitatory neurotransmitter systems proved capable of dose dependently blocking these seizures, i.e., the anticholinergic drug biperiden (ED50 12 mg/kg i.p.), the excitatory amino acid antagonist (+/-)-2-amino-7-phosphonoheptanoic acid (120 mg/kg), the gamma-aminobutyric acid (GABA) agonists muscimol (0.66 mg/kg), 4,5,6,7-tetrahydroisoxazolo(5,4-c) pyridine-3-ol (1.3 mg/kg), progabide (50 mg/kg) and its acidic metabolite SL 75102 (45 mg/kg), the GABA aminotransferase inhibitors aminooxyacetic acid (0.9 mg/kg), gamma-acetylenic GABA (2.1 mg/kg) and ethanolamine-O-sulfate (1000 mg/kg), the GABA uptake inhibitor (-)-nipecotic acid ethyl ester (21 mg/kg), the dopamine agonist apomorphine (approximately 5 mg/kg), the dopamine precursor 3,4-dihydroxy-L-phenylalanine (34 mg/kg), and the alpha-adrenoceptor agonists clonidine (0.38 mg/kg) and xylazine (approximately 10 mg/kg). The anticonvulsant effect of 3,4-dihydroxyl-L-phenylalanine was not significantly affected by pretreatment with the dopamine-beta-hydroxylase inhibitors disulfiram and diethyldithiocarbamate, thus strongly indicating that 3,4-dihydroxyl-L-phenylalanine was acting through increase in dopamine rather than noradrenaline levels in the brain. The (+)-isomer of nipecotic acid ethyl ester, the glycineamide derivative milacemide, the indirect 5-hydroxytryptamine agonist fenfluramine and the 5-hydroxytryptamine antagonist ketanserin exerted no anticonvulsant action. The 5-hydroxytryptamine precursor L-5-hydroxytryptophan and the dopamine agonist lisuride were only weakly active but exerted pronounced side effects in the animals. Weak anticonvulsant effects were also determined for atropine, the noradrenaline precursor DL-threo-3,4-dihydroxyphenylserine and the excitatory amino acid antagonist (+/-)-2-amino-5-phosphonopentanoic acid. Comparison of anticonvulsant potencies of the various drugs in gerbils with potencies reported in other genetic animal models of epilepsy, such as audiogenic seizure-susceptible mice, indicated that drugs that increase GABA and dopamine levels in the brain are strikingly more effective in gerbils than in other species in blocking generalized seizures.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Influence of pharmacological manipulation of inhibitory and excitatory neurotransmitter systems on seizure behavior in the Mongolian gerbil. 285 79

GABA-gated chloride ion influx was measured in brain 'microsac' preparations of young (20-22-day-old) and older (40-42-day-old) C57BL6J and DBA2J mice. The young DBA2J mice are susceptible to audiogenic seizures. GABA sensitivity was reduced in young DBA2J mice as compared to age-matched C57BL6J mice or older mice of either strain. Age and strain differences in ligand binding to GABA/benzodiazepine receptor complex and glutamate receptor could not account for this finding. These results provide evidence for a defect in GABA-gated chloride ion influx in audiogenic seizure-susceptible DBA2J mice.
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PMID:GABA-gated chloride ion influx and receptor binding studies in C57BL6J and DBA2J mice. 288 95

The progression of sound-induced seizures was examined in unilaterally or bilaterally sensitized SJL/J mice tested either monaurally or binaurally. An unexpected right-side advantage for becoming susceptible to audiogenic seizure was observed. In addition, two distinct patterns of seizure progression were noted, a uniphasic sequence in which a single burst of running preceded the convulsion and a biphasic pattern with two such bursts. The biphasic progression is viewed to be the result of unilaterally initiated seizures and characteristically reached only a clonic level of severity. Uniphasic seizures are concluded to be the result of bilaterally initiated seizures and, when they occurred after more than 30 s of auditory stimulation, frequently reached a tonic level of intensity. The present results support the view that audiogenic seizures are characterized by precisely timed, sequential processes dependent upon the specific priming and test procedures employed.
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PMID:Monaural and binaural audiogenic seizures in mice. 293 Apr 32

Despite intense investigation, the role of serotonergic neurons in audiogenic seizures in mice remains uncertain. In the work reported here, audiogenic seizure susceptibility and brain tryptophan and serotonin concentrations were measured in DBA/2J mice after administration of three doses of L-tryptophan or p-chlorophenylalanine. p-Chlorophenylalanine reduced brain serotonin and significantly prolonged the latency to appearance of all seizure phases. L-tryptophan was largely ineffective in protecting against seizures and in elevating brain serotonin content, despite the fact that it caused a marked increase in brain tryptophan content. Thus, it appears that DBA/2J mice have an impaired ability to synthesize serotonin from tryptophan.
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PMID:Audiogenic seizures and brain serotonin after L-tryptophan and p-chlorophenylalanine. 293 72

CGS 9896, a pyrazoloquinoline that potently binds to benzodiazepine receptors, has been reported to have anticonflict activity in conventional footshock paradigms and to antagonize pentylenetetrazol-induced seizures. In the present experiments, the pentylenetetrazol discriminative cue was blocked by CGS 9896 with a potency comparable to that of diazepam. CGS 9896 also selectively lengthened the latency to terminate self-initiated brain stimulation reward. These procedures extend the anxiolytic activity of CGS 9896 to models that do not rely upon footshock-induced conflict. CGS 9896 did not impair the traction reflex in mice, did not impair rotorod performance in rats, did not reduce unpunished operant responding and decreased motor activity only slightly, indicating no distinguishable sedation or muscle relaxation in rodent models. In fact, diazepam-induced rotorod impairment was blocked by CGS 9896. The anticonvulsant effects of CGS 9896, as indicated by audiogenic seizure and pentylenetetrazol-induced seizure studies, were substantial but were weaker than those of diazepam, possibly because of the muscle relaxant component of diazepam. Ethanol-induced motor impairment was potentiated more markedly by diazepam than by CGS 9896. Mixed agonist-antagonist properties of CGS 9896 therefore emerge when a comprehensive battery of behavioral assessments is utilized. CGS 9896 may have clinical anxiolytic activity without sedation or muscle relaxation.
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PMID:CGS 9896: agonist-antagonist benzodiazepine receptor activity revealed by anxiolytic, anticonvulsant and muscle relaxation assessment in rodents. 299 50


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