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

This study better defines the way in which the thalamus controls expression of experimental generalized seizures. The effects of small intrathalamic injections of the direct GABA agonist muscimol on the thresholds of pentylenetetrazol (PTZ)-induced seizures and on spontaneous behavior were determined in the rat and compared with the effects of injections of gamma-vinyl-GABA (GVG), an irreversible inhibitor of GABA transaminase. Muscimol injections produced neuronal inhibition in a relatively small area of thalamus, whereas GVG injections produced inhibition in a much larger area. Muscimol injections in the midline thalamus in the vicinity of the paraventricular, paratenial, interanteromedial, intermediodorsal, and central medial nuclei facilitated PTZ myoclonic and clonic seizures and also produced sedation. These effects on seizure thresholds were attributable both to a lower PTZ threshold dose for initiation of electroencephalographic (EEG) seizure activity and to an increased probability of this EEG activity being expressed as behavioral seizures. Midline injections located more posteriorly in the thalamus also inhibited tonic seizures. Muscimol injections placed laterally, dorsally, or ventrally to this midline thalamic region had much less effect on behavior or seizures. In contrast, GVG injections in the anterior medial thalamus elevated the threshold for all PTZ seizure types and for associated EEG seizure activity but had little effect on spontaneous behavior. These findings demonstrate the existence of an important seizure regulatory system in the midline of the thalamus and a direct anatomic link between the mechanisms for regulating arousal and seizure production which may help explain the association between sleep and seizure facilitation in humans.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Identification of a median thalamic system regulating seizures and arousal. 275 1

The effects of chronic cortical seizures on the autoradiographic distributions of two markers of the gamma-aminobutyric acid (GABA)/benzodiazepine receptor--chloride ionophore complex within local and long circuits connected to the focus were examined. Rats were subjected to electrically triggered seizures of the forelimb--sensorimotor overlap zone either daily or once every other day. At the time of sacrifice the rats had received a mean of 39 +/- 3 stimulations and their seizure responses had grown in intensity and duration. [3H]Muscimol binding and [3H]flunitrazepam binding, at near saturating ligand concentrations were unchanged in the focus, mirror focus, dorsolateral caudate, globus pallidus, ventrolateral and ventrobasal thalamic nuclei, and the substantia nigra pars reticularis. These results indicate that the progressive increases in strength and duration of recurrent focal cortical seizures are not accompanied by changes in the density of either GABA receptors or benzodiazepine receptors within the focus or projection pathways.
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PMID:Effects of chronic cortical seizures on GABA and benzodiazepine receptors within seizure pathways. 283 19

The effects of atropine (5 mg/kg), baclofen (10 mg/kg), gamma-hydroxybutyrate (300 mg/kg), gamma-butyrolactone (100 mg/kg) and muscimol (1 mg/kg) upon the action of 2-amino-5-phosphonovalerate (APV; an antagonist at receptors for N-methyl-D-aspartate) on the threshold current for seizures induced by electroshock, were studied in mice. Neither APV, up to 100 mg/kg, nor the other agents produced any significant increase in the convulsive threshold when tested alone. Muscimol had no effect on the action of APV (50 and 100 mg/kg) and the combination of APV with the subthreshold doses of atropine, baclofen, gamma-hydroxybutyrate and gamma-butyrolactone resulted in a clearcut anticonvulsant action. The observed increases in the threshold may be due to the suppressant effects of the drugs upon excitatory transmission, which eventually leads to the potentiation of the action of APV, resulting from blockade of N-methyl-D-aspartate receptors.
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PMID:Modification of the anticonvulsant activity of 2-amino-5-phosphonovalerate by agents affecting different neurotransmitter systems. 286 64

The effects of three specific GABA receptor agonists, muscimol, progabide, and gaboxadol, on kindled seizures were evaluated in amygdala-kindled rats. The only compound that exerted significant anticonvulsant effects at nonsedative doses was progabide. Thus, after i.p. administration of 100 mg/kg progabide, a significant increase in seizure latency and significant decreases in duration of motor seizures and amygdala afterdischarges were determined. A decrease in severity of motor seizures was found only after 200 mg/kg progabide which, however, gave rise to marked sedation and muscle relaxation. Muscimol and gaboxadol were almost inactive in attenuating kindled seizures even at doses that produced pronounced side effects. Assuming that the amygdala-kindled rat is a useful model of complex partial seizures with secondary generalization in the human, the data suggest that GABA receptor agonists are not effective against this type of epilepsy (muscimol, gaboxadol) or effective only at large doses (progabide).
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PMID:Evaluation of different GABA receptor agonists in the kindled amygdala seizure model in rats. 299 Sep 87

Motor limbic seizures occur following a systemic injection of pilocarpine (380 mg/kg) in rats. Focal injection of the selective N-methyl-D-aspartate receptor antagonist, (+/-)-2-amino-7-phosphonoheptanoic acid (2-APH, 5-20 pmol), bilaterally into the entopeduncular nucleus (EP) prior to pilocarine blocks these seizures. Muscimol (50 pmol), a potent gamma-aminobutyric acid receptor agonist, injected bilaterally into EP produces a similar protection against pilocarpine-induced seizures. Thus by blocking excitatory neurotransmission or facilitating inhibition within the EP, the severity of limbic seizures can be reduced.
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PMID:2-Amino-7-phosphonoheptanoic acid (2-APH) infusion into entopeduncular nucleus protects against limbic seizures in rats. 300 43

The effects of microinjection of various neuroactive compounds into the anterior thalamic nucleus (AN) and other selected subcortical regions of guinea pig brain on the expression of pentylenetetrazol (PTZ)-induced behavioral and electrical seizure activity were examined. Excitatory agents, kainic acid (KA), bicuculline (BIC) or PTZ, injected into the AN or other thalamic nuclei, striatum, but not the mammillary bodies (MB), facilitated the EEG convulsant action of systemically administered PTZ. Injection of muscimol into the AN protected against the expression of PTZ-induced repetitive high-voltage EEG seizure discharges and inhibited the facilitatory effects of subcortically applied KA or BIC. Injection of muscimol into the AN was also able to terminate established ongoing seizure discharges. Unilateral application of muscimol to the AN did not prevent the repetitive hypersynchronous EEG discharges following systemic PTZ but did result in the delay in the onset of cortical hypersynchrony in the ipsilateral hemisphere. Muscimol injections into other thalamic nuclei, MB, cortex, striatum or directly into the CSF space had no anticonvulsant effect, however. Microinjection of gamma-vinyl-gamma-aminobutyric acid, a selective GABA transaminase inhibitor, resulted in protection from the behavioral convulsant action and lethal effects of PTZ when administered into the thalamus, especially the AN, but not when injected into the striatum or CSF. These data demonstrate that the AN is an important subcortical nucleus for the mediation of both cortical EEG synchrony and behavioral seizure expression induced by PTZ. In light of previous results establishing a role for the brainstem and diencephalon in PTZ seizure expression, the AN may serve, in part, as a gating mechanism for the propagation of paroxysmal activity between subcortical areas and the cerebral cortex.
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PMID:Anterior thalamic mediation of generalized pentylenetetrazol seizures. 354 79

Bicuculline methiodide (0.5-3 nmol) and picrotoxin (0.5-4 nmol) were injected uni- or bilaterally into the rat amygdala and the resulting behavioural, electroencephalographic and morphological alterations were studied. In rats treated unilaterally with lowest doses of either bicuculline or picrotoxin (0.5 and 1 nmol) increase in the locomotor activity, occasional myoclonus of the hindlimbs and wet dog shakes were observed. At doses of 2-3 nmol, both gamma-aminobutyrate antagonists produced a sequence of repetitively occurring behavioural alterations including limbic gustatory automatisms, tremor and myoclonus of the forelimbs, head nodding and rearing, that developed over 15-30 min and built up progressively into the recurrent motor limbic seizures lasting for 1-6 h. In animals injected bilaterally with either bicuculline (0.5-3 nmol) or picrotoxin (0.5-3 nmol) motor limbic seizures rapidly developed into the status epilepticus lasting for several hours. Bicuculline and picrotoxin produced both ictal and interictal epileptiform activity in the electroencephalogram. A spectrum of electroencephalographic changes consisted of high voltage fast activity, slow and fast voltage spiking, paraoxysmal bursts and periods of postictal depression. The earliest electrographic alterations appeared in the amygdala and then rapidly spread to cortical areas. Electrographic seizures started 1-10 min after unilateral injections of large doses of bicuculline and pictrotoxin (2-4 nmol). Ictal periods lasted for 1-2 min, recurred every 5-10 min and were followed by periods of depression of the electrographic activity. Bilateral injections of large doses of both gamma-aminobutyrate antagonists (2-3 nmol) resulted in the status epilepticus. Morphological examination of frontal forebrain sections with light microscopy revealed a widespread damage to the amygdala, olfactory cortex, substantia nigra, thalamus, hippocampus and neocortex. Pretreatment of animals with diazepam prevented the build-up of convulsive activity and brain damage produced by bicuculline or picrotoxin. Muscimol retarded the appearance and shortened the duration of convulsive activity, but did not alter the sequence and intensity of seizures. The results indicate that gamma-aminobutyrate antagonists, bicuculline and picrotoxin when directly applied to the amygdala can elicit in rats motor limbic seizures, epileptic changes in the electroencephalogram indicative of repetitive limbic seizures, and status epilepticus accompanied by seizure-related brain damage.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Injections of picrotoxin and bicuculline into the amygdaloid complex of the rat: an electroencephalographic, behavioural and morphological analysis. 397 84

DMCM (methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate) is a very potent convulsant with high affinity for specific benzodiazepine binding sites. A number of compounds were compared for their ability to prevent seizures induced by DMCM and pentylenetetrazol. DMCM seizures were antagonized by benzodiazepine (BZ) receptor antagonists, such as Ro 15-1788, CGS 8216 and several beta-carboline-3-carboxylates, which all fail to inhibit pentylenetetrazol seizures. The benzodiazepines diazepam, clonazepam and lorazepam as well as valproate, ethosuximid, phenobarbital, primidone, diphenylhydantoin and carbamazepine antagonized both DMCM and pentylenetetrazol. Muscimol and gamma-vinyl-GABA did not inhibit DMCM seizures whereas THIP showed a weak and selective effect against DMCM. Valproate showed a relatively potent (60 mg/kg i.p.) and competitive antagonism of short duration. Baclofen antagonized DMCM at 3 mg/kg. Valproate and baclofen were at least 5 times more potent against DMCM-induced than against pentylenetetrazol-induced seizures. DMCM most probably induces the seizures by selective impairment of the functions mediated by the GABA/BZ receptor-chloride channel complex (inverse agonism) and therefore differs from GABA receptor blockers.
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PMID:DMCM: a potent convulsive benzodiazepine receptor ligand. 631 96

Ro 5-4864 (4'-chlorodiazepam) elicited convulsions in mice with a CD50 of 23.5 mg/kg (i.p.) and increased the firing rate of substantia nigra zona reticulata neurons in a dose dependent fashion (0.5-4 mg/kg i.v.). Diazepam and clonazepam, but not Ro 15-1788, were potent inhibitors of Ro 5-4864 induced convulsions. Ro 15-1788 was also ineffective in reversing Ro 5-4864 induced increases in cell firing of zone reticulata neurons. Muscimol potently inhibited the seizures and reversed increases in cell firing elicited by Ro 5-4864. Phenobarbital and pentobarbital inhibited Ro 5-4864 induced convulsions with moderate potencies, while phenytoin and carbamazepine were ineffective at doses of up to 100 mg/kg. These observations suggest that Ro 5-4864 does not elicit its pharmacologic actions through a direct action at a 'brain-type' benzodiazepine receptor. However, both the profile and potency of compounds effective in inhibiting the electrophysiological and pharmacological effects of Ro 5-4864 suggest that this compound may act by perturbation of a component of the GABA-benzodiazepine receptor chloride ionophore complex. These findings do not, however, rule out a direct involvement of the high affinity 'peripheral-type' benzodiazepine receptors found in brain.
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PMID:Electrophysiological and pharmacological actions of the convulsant benzodiazepine Ro 5-4864. 632 93

Certain Wistar rats from our laboratory colony present genetically determined seizures similar to human petit-mal absences. Muscimol, THIP and L-baclofen, agonists of GABA receptors, and gamma-vinyl GABA (GVG), an inhibitor of GABA degradation, enhanced the duration of spontaneous petit-mal-like seizures in a dose-dependent fashion. These findings raise questions as to the role of GABAergic neurotransmission in the occurrence of this type of spontaneous spike and wave discharges.
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PMID:Enhancement of spike and wave discharges by GABAmimetic drugs in rats with spontaneous petit-mal-like epilepsy. 642 42


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