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)

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

The role of the inferior colliculus and GABAeric transmission within this structure in the development of susceptibility to sound-induced seizures in ethanol-dependent rats was examined. Ethanol-dependent rats with bilateral electrolytic lesions which destroyed approximately 50.0 +/- 6.4% of the inferior colliculus failed to exhibit susceptibility to sound-induced seizures. However, comparable medial geniculate body lesions (82.7 +/- 2.7% complete) did not alter wild running, slightly reduced tonus and actually increased clonus susceptibility in rats treated similarly with ethanol. As reported previously, bilateral injection of either muscimol (43-263 pmol/site) or racemic baclofen (520-1580 pmol/site) into the inferior colliculus also suppressed seizure susceptibility. Other studies in ethanol-naive animals found that bilateral microinfusion of (+)-bicuculline methiodide (2 or 20 pmol/min for up to 5 min) into the inferior colliculus induced wild running and clonus closely resembling sound-induced seizure responses in ethanol-dependent rats. Although similar microinjections of (+)-bicuculline methiodide (0.4 pmol/min for 5 min) into the inferior colliculus did not induce seizure activity directly, an increased susceptibility to sound-induced seizures was observed. Electrolytic lesions of the medial geniculate body did not block wild running responses induced by (+)-bicuculline methiodide, but slightly reduced clonus. Five-minute infusions of picrotoxin (200 pmol/min), Ro5-3663 (2000 pmol/min), kainic acid (20 or 200 pmol/min), strychnine (2000 pmol/min) or carbachol 2000 pmol/min) into the inferior colliculus of ethanol-naive rats all induced bicuculline-like seizures. Seizures induced by bicuculline methiodide, picrotoxin or Ro5-3663 occurred within 5 min after the start of infusions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:GABAergic modulation of inferior colliculus excitability: role in the ethanol withdrawal audiogenic seizures. 300 88

The effects of selected modulators of GABAergic transmission, either alone or in combination, were tested for their potency on the seizure pattern and mortality induced by convulsant drugs in rat. Pentobarbital and diazepam were effective against both tonic and clonic seizure components induced by bicuculline and picrotoxin. The anticonvulsant profile of ethanol closely resembled that of pentobarbital. Pentobarbital, diazepam and ethanol did not modify seizures induced by strychnine. In contrast, progabide, a central gamma-aminobutyric acid (GABA) receptor agonist, caused significant protection only against convulsions induced by strychnine and its lethality, but did not protect against seizures induced by bicuculline or picrotoxin. Data on interaction of drugs with subprotective doses of these agents clearly demonstrated potentiation of the anticonvulsant actions of these modulators. Thus, seizures induced by bicuculline were more sensitive to the inhibition by pentobarbital in combination with diazepam or ethanol, while pentobarbital with progabide was equally effective against convulsions induced by GABA antagonists. Diazepam, in combination with progabide, blocked only convulsions induced by picrotoxin. Ethanol, in combination with either pentobarbital or with diazepam, was effective against all the three convulsant drugs. These results are consistent with the concept that drugs which facilitate GABAergic transmission are effective against seizures related to an impairment of GABA transmission. Further, the present data indicate that tonic seizures are more susceptible to the actions of drugs than the clonic component. Smaller doses of these drugs, alone or in combination, modified the seizure patterns and mortality, whereas at larger doses, the possible involvement of a nonspecific depressant action cannot be ruled out.
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PMID:Anticonvulsant profile of drugs which facilitate GABAergic transmission on convulsions mediated by a GABAergic mechanism. 301 Jan 61

Ethanol (1.5 g/kg) administered intraperitoneally to kindled rats blocks the seizures normally elicited by electrical stimulation of the amygdala. Tolerance to this anticonvulsant effect develops following a series of ethanol injections delivered at 48-hr intervals only when an amygdaloid stimulation is administered during each period of ethanol intoxication. In the present study, the response contingency was shown to also play a critical role in the dissipation of tolerance. There was no significant loss of tolerance over a 14-day retention interval in rats that received: 1) bidaily ethanol injections each followed 1 hr later by a convulsive stimulation; or 2) bidaily ethanol injections but no stimulation; or 3) neither ethanol nor stimulation. In contrast, tolerance dissipated completely in rats that received: 1) bidaily stimulations but no ethanol; or 2) convulsive stimulation 1 hr before each bidaily ethanol injection. Accordingly, the cessation of ethanol exposure was neither necessary nor sufficient for the dissipation of tolerance to the anticonvulsant effect of ethanol. The critical factor in the decline of tolerance was the elicitation of seizures in the absence of ethanol.
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PMID:Response contingency and the dissipation of ethanol tolerance. 342 10

RO 15-4513, an imidazodiazepine that has been reported to reverse some of the behavioral effects of ethanol, was given to DBA/2 mice. Although no animals treated with a 6 mg/kg dose of this drug had seizures, 20% of animals given 20 mg/kg of this drug had tonic seizures. Ethanol withdrawal was induced in DBA/2 mice treated with 4-methyl pyrazole using an inhalation paradigm. Mice were more likely to have a seizure during ethanol withdrawal if treated with RO 15-4513 (6 mg/kg) than if they received the vehicle. These data suggest administering RO 15-4513 as an alcohol antagonist to alcoholic subjects may increase the incidence of seizures.
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PMID:RO 15-4513 induces seizures in DBA/2 mice undergoing alcohol withdrawal. 367 63

Exposure of the mammalian fetus to ethanol causes a variety of nervous system abnormalities, but the evidence relating to seizure susceptibility is contradictory. Therefore, offspring of rat dams that had consumed a mean of 6.9 g/kg/day of ethanol were compared with pair-fed and free-fed controls on rate of electrical kindling of the amygdala and on open field measures of activity. The Ethanol-exposed males displayed increased ambulation and the Ethanol females displayed increased rearing and defecation in an open field. However, there was no significant difference between the groups in rate of kindling. Although the gross size of the brains measured on a coronal section through the anterior tip of the hippocampus did not differ significantly among the groups, there was a highly significant reduction in percent brain tissue area and a corresponding increase in percent ventricle area in the Ethanol group.
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PMID:Prenatal ethanol exposure alters rat brain morphology but does not affect amygdaloid kindling. 380 76

Female chicks carrying the lethal, sex-linked recessive paroxysmal (px) gene are susceptible to spontaneous and audiogenic seizures. Because seizure activity does not begin until 1 to 2 weeks posthatching - coincidental with disappearance of the yolk-sac - it is postulated that a contributing factor to seizure activity may be a developmental failure of the chick's ability to switch from lipid to carbohydrate as a primary energy source. In testing this hypothesis, three experiments were performed: 1) to evaluate cerebral energy reserves - adenosine triphosphate (ATP), phosphocreatine - of px and normal chicks; 2) to determine effects of energy source (ethanol, glucose, insulin, and glucose-insulin combined) on audiogenically-induced seizure activity and electrical seizure threshold; 3) to evaluate energy source utilization as estimated by the respiratory quotient (RQ). Brain ATP and phosphocreatine levels in px chicks were both decreased (P less than .05) as early as 10 days posthatching. Ethanol increased electrical seizure threshold in 50% of px chicks and provided protection from audiogenic stimulation. No consistent effect was found with any of the other substances. The RQ of px chicks were lower (P less than .05) than those of controls by 18 days posthatching.
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PMID:Energy metabolism in audiogenically seizure-prone chicks. 388 94

Ethanol (1.5 g/kg) administered intraperitoneally to kindled rats blocked the seizures normally elicited in these subjects by electrical stimulation of the amygdala. Tolerance to this anticonvulsant effect developed following a series of ethanol intubations delivered at 48-hr intervals only when an amygdaloid stimulation was administered during each period of ethanol intoxication. Subjects stimulated 1 hr following each intubation were tolerant to the intraperitoneal test dose after only five intubations (2 g/kg), whereas those stimulated 1 hr prior to each intubation displayed no tolerance during the course of 20 such trials. Even at high intubation doses (5 g/kg), significant levels of tolerance to the anticonvulsant effect of the intraperitoneal test dose were not observed in subjects unstimulated during each period of post-intubation intoxication. These findings emphasize the important role of response contingency in ethanol tolerance; tolerance develops readily for only those effects of alcohol that repeatedly manifest themselves during the periods of ethanol exposure.
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PMID:Contingent tolerance to the anticonvulsant effects of alcohol. 402 70

Ethanol (2.0-5.0 g/kg, IP) caused a dose-related impairment of the aerial righting reflex of mice 60 min after injection. Ethanol (3.5 g/kg, IP) given simultaneously with neurotensin (30 micrograms, IC), bombesin (30 micrograms, IC) or beta-endorphin (20 micrograms, IC) caused a greater impairment of the reflex than ethanol alone. Simultaneous treatment with ethanol (4.0 g/kg, IP) and thyrotropin-releasing hormone (TRH, 3.0-30 micrograms, IC) caused less impairment of this measure than ethanol alone. None of the peptides altered the height of aerial righting when administered alone, or when administered with ethanol no peptide altered blood or brain ethanol content. Unexpectedly, TRH (20 and 40 mg/kg, IP) potentiated the action of ethanol by increasing punished licking in water-deprived rats, rather than antagonizing this acute action of ethanol. Like ethanol (1.0 and 2.0 g/kg, IP), beta-endorphin (100 micrograms, IC) suppressed ethanol-withdrawal tremor and audiogenic-seizure susceptibility in ethanol-dependent rats. beta-Endorphin (1 microgram) and bombesin (10 and 30 micrograms, IC) reduced only audiogenic-seizure susceptibility. TRH (10-100 micrograms, IC, or 1-40 mg/kg, IV) and neurotensin (10-100 micrograms, IC) had no effect on these ethanol-withdrawal signs. These findings suggest that centrally active peptides may play a role in certain acute and chronic actions of ethanol. Because TRH, neurotensin, bombesin and beta-endorphin do not alter all actions of ethanol in the same way, an interaction of ethanol with many functionally independent neuronal circuits is suggested.
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PMID:Modification of the actions of ethanol by centrally active peptides. 626 62

We are selectively breeding mice prone (WSP) and resistant (WSR) to ethanol withdrawal seizures assessed by handling induced convulsions (HIC). The possibility that differences between the lines in HIC scores are a result of differences in general CNS excitability not specific to ethanol withdrawal was examined. Using treatments which produce generalized seizures (electroconvulsive shock, strychnine, and flurothyl) and gamma amino-butyric acid (GABA) antagonists (picrotoxin, bicuculline, and pentylentetrazol), the ED50 for seizures was determined in the selected lines. In addition, the sensitivity of WSP and WSR mice to the anticonvulsant actions of ethanol against each treatment was determined. Neither the convulsant amperage 50 (CA50) for ECS nor the ED50 for any drug treatment differed for the selected lines. When ethanol (1.5 g/kg) was administered prior to ECS, there was a dramatic differential suppression of ECS in the lines: the CA50 of WSR mice was elevated 5-fold, whereas the CA50 of WSP mice increased only two fold. Ethanol pretreatment also elevated the ED50 for strychnine and flurothyl in WSR mice significantly more than WSP mice, but the line difference was smaller than for the anticonvulsant effect against ECS. The ED50s for the GABA antagonists were not different between the WSR and WSP lines after ethanol pretreatment. We conclude that genetic selection is producing lines of mice that differ specifically in the degree of seizure severity caused by withdrawal from ethanol physical dependence and not in generalized CNS excitability. An increased sensitivity to the anticonvulsant effects of ethanol against some convulsant treatments has appeared as a correlated response to selection in the WSR line.
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PMID:Specific ethanol withdrawal seizures in genetically selected mice. 654 39


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