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

In experiments on albino mice with pentylenetetrazol convulsions it has been found that GABA, introduced intracerebroventricularly in a dose of 100 microgram/mouse, has a marked anticonvulsive effect. Scopolamine in doses of 1, 10 and 50 mg/kg i. p. does not influence significantly the convulsive-seizure reactions, while spasmolytin inhibits them only in large doses (80 mg/kg weight). The inhibitory effect of GABA does not change significantly on the background of scopolamine, while spasmolytin in a dose of 50 mg/kg (and to a lesser extent 80 mg/kg) antagonizes the inhibitory effect of GABA. Arecoline in doses of 1 and 10 mg/kg inhibits to a certain extent the convulsive-seizure reactions, and in doses of 10 mg/kg it potentiates the effect of GABA. Physostigmine in doses of 0.1 and 0.5 mg/kg has no significant effect, while in a dose of 0.3 mg/kg its effect is inhibitory. On the background of the two higher physostigmine doses, however, the anticonvulsive effect of GABA is markedly decreased. The results show that changes in the functional activity level of the brain cholinergic systems lead to changes in the inhibitory effect of GABA on the convulsive reactivity. The mechanisms of these correlations are complex. However, the results are in support of the view that the balance between the different neurotransmitter systems in the brain and not a separate specifically responsible neurotransmitter system, are of decisive significance for the convulsive excitability and reactivity.
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PMID:On some relationships between gamma-aminobutyric acid (GABA) and the cholinergic mechanisms in pentylenetetrazol convulsions. 61 63

Chronic pharmacological experiments were conducted to evaluate the relationship between sensitization induced by repeated administration of amphetamine (AMPH) and electrical stimulation of the amygdala. While AMPH withdrawal did not influence the kindling process, AMPH administered during the kindling procedure increased the rate at which seizures evolved, and under these conditions withdrawal from chronic AMPH further facilitated the propensity to kindle. Haloperidol (HAL) treatment failed to block the stimulant-induced increase in kindling acquisition indicating that changes in dopamine (DA) are not necessary for the AMPH/kindling synergism to develop. Scopolamine dose-dependently retarded kindling evolution irrespective of prior AMPH pretreatment also ruling out a cholinergic mechanism in the kindling sensitization. Subsequent experiments assessed the interactive effects of AMPH and desipramine (DMI) on the kindling process. Animals chronically exposed to AMPH and switched to DMI treatment during the kindling procedure kindled faster than control subjects. In addition, withdrawal from DMI preexposure advanced the AMPH-induced increase in kindling rate. These results were discussed in terms of the role of norepinephrine-mediated inhibition of the kindling process, and were related to drug-elicited alterations in beta-adrenergic receptor functioning. Taken together, these findings implicate the amygdala as an important structure in the development of non-DA forms of AMPH sensitization.
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PMID:Amphetamine sensitization and amygdala kindling: pharmacological evaluation of catecholaminergic and cholinergic mechanisms. 164 66

Scopolamine (Hyoscine), an anticholinergic compound is widely used for the prophylaxis and treatment of motion sickness and might be used with oxygen diving and hyperbaric oxygen therapy. We therefore decided to test the interaction of scopolamine with oxygen at high pressure. Thirty-six rats implanted with cortical EEG electrodes were injected subcutaneously with two doses of scopolamine (0.02 or 0.2 mg.kg-1), or the vehicle (saline), 30 min before exposure to 5 atm abs (0.5 MPa) oxygen. Electroencephalogram and heart rate were monitored continuously. Spectral analysis of the EEG was carried out, and the duration of the latent period before convulsions was determined. No significant difference was found in the duration of the latent period between the control rats receiving vehicle (saline) and rats injected with scopolamine (n = 12 for each group). Changes in background EEG activity and maximal dilation of the pupil were detected at both scopolamine doses. Heart rate significantly decreased at 0.02 mg.kg-1 and increased at the dose of 0.2 mg.kg-1 scopolamine. Our findings indicate that the duration of the latent period preceding hyperoxic seizures is not altered by scopolamine in rats; however, other side effects of the drug regarding visual and cardiovascular symptoms should be considered when scopolamine is used in combination with hyperbaric oxygen.
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PMID:Hyperbaric oxygen and scopolamine. 185 67

The effect of central serotonergic stimulation on hippocampal and neocortical electrical activity and behavior was studied in freely moving rats by administering: (a) tranylcypromine followed by tryptophan, (b) fluoxetine followed by 5-hydroxytryptophan, or (c) p-chloroamphetamine alone. In all rats, scopolamine-resistant hippocampal rhythmical slow activity (RSA), thought to be dependent on brain serotonin, maintained its normal relation to behavior, occurring in close correlation with Type 1 behaviors (postural changes, turning of the head, walking). This RSA was generally absent during stereotyped behavior (head weaving, forepaw treading, hindlimb splaying and tremor). Scopolamine-resistant neocortical low-voltage fast activity (LVFA), also though to be dependent on brain serotonin, was present during Type 1 behaviors and also during stereotyped behavior. Most rats that developed a full stereotyped behavior syndrome had behavioral and electrocortical seizures which were associated with a reduction in the amplitude of hippocampal activity. These seizures were suppressed by methysergide or benserazide. Metergoline (and methysergide to a lesser extent) suppressed the stereotypic behaviors of the serotonin syndrome, resulting in a striking increase in the locomotion caused by central serotonergic stimulation. Such locomotion was accompanied by RSA and LVFA. It was concluded that increased serotonergic activity in the CNS causes an increase in motor activity and a correlated increase in scopolamine-resistant hippocampal RSA and scopolamine-resistant neocortical LVFA and suggested that metergoline blocks serotonin receptors mediating stereotyped behaviors, thereby permitting the expression of serotonin-mediated locomotion.
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PMID:The effects of serotonergic stimulation on hippocampal and neocortical slow waves and behavior. 193 39

Scopolamine and naloxone were administered singly and in combination to different groups of rats undergoing electrical kindling of the amygdala. Scopolamine significantly reduced the maximal seizure stage attained during 15 drug sessions and increased the total number of afterdischarges required to kindle a generalized convulsion. Naloxone had a similar but weaker and nonsignificant effect. The results confirm that antagonism of muscarinic receptors by scopolamine retards amygdala kindling.
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PMID:Effects of treatment with scopolamine and naloxone, singly and in combination, on amygdala kindling. 355 20

Microinjections of the cholinergic agonists, carbachol and bethanechol, either into the amygdala or into the dorsal hippocampus produced sustained limbic seizures and brain damage in rats. Systemic administration of pilocarpine in rats resulted in a sequence of convulsive disorders and widespread brain damage as well. Scopolamine prevented the development of convulsive activity and brain damage produced by cholinomimetics. These results suggest that the excessive stimulation of cholinergic muscarinic receptors can lead to limbic seizures and brain damage. It is postulated that muscarinic cholinergic mechanisms are linked to the etiology of temporal lobe epilepsy and epileptic brain damage.
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PMID:Cholinomimetics produce seizures and brain damage in rats. 614 Jan 82

Increasing doses of pilocarpine, 100-400 mg/kg, were given intraperitoneally to mice and the resulting behavioral, electroencephalographic and neuropathological alterations were studied. No behavioral phenomena were observed in mice treated with the lowest dose of pilocarpine. Occasional tremor and myoclonus of hindlimbs were found in animals which received pilocarpine in a dose of 200 mg/kg. At doses of 300, 325 and 350 mg/kg, pilocarpine produced a sequence of behavioral alterations including staring spells, limbic gustatory automatisms and motor limbic seizures that developed over 15-30 min and built up progressively into a limbic status epilepticus lasting for several hours. The highest dose of pilocarpine, 400 mg/kg, was generally lethal to mice. Pilocarpine produced both interictal and ictal epileptiform activity in the electroencephalogram (EEG). The earliest EEG alterations appeared in the hippocampus and then spread to cortical areas. EEG seizures started 10-15 min after injection of large doses of pilocarpine, 300-350 mg/kg. Ictal periods lasted for 1-2 min, recurred every 5-10 min and were followed by periods of depression of the EEG activity. By 30-45 min paroxysmal activity resulted in a status epilepticus. Examination of frontal forebrain sections with light microscopy revealed a widespread damage to several brain regions including the hippocampus, amygdala, thalamus, olfactory cortex, neocortex and substantia nigra. Scopolamine, 10 mg/kg, and diazepam, 10 mg/kg, prevented the development of convulsive activity and brain damage produced by pilocarpine. The results emphasize that excessive and sustained stimulation of cholinergic receptors can lead to seizures and seizure-related brain damage in mice. It is proposed that systemic pilocarpine in mice provides a useful animal model for studying mechanisms of and therapeutic approaches to temporal lobe epilepsy.
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PMID:Seizures produced by pilocarpine in mice: a behavioral, electroencephalographic and morphological analysis. 649 17

Anticholinergics, benzodiazepines and N-methyl-D-aspartate (NMDA) antagonists have been shown to modulate the expression of nerve agent-induced seizures. This study examined whether the anticonvulsant actions of these drugs varied depending on the duration of prior seizure activity. Rats implanted with electrodes to record electroencephalographic (EEG) activity were pretreated with the oxime HI-6 (125 mg/kg, IP) to prolong survival, and then challenged with a convulsant dose of the nerve agent soman (180 micrograms/kg, SC); treatment compounds (scopolamine, diazepam, MK-801, atropine, benactyzine, and trihexyphenidyl) were delivered IV at specific times after seizure onset. Both diazepam and MK-801 displayed a similar profile of activity: At both short or long times after seizure initiation the anticonvulsant efficacy of each drug remained the same. Diazepam, and especially MK-801, enhanced the lethal actions of soman by potentiating the respiratory depressant effects of the agent; scopolamine given prior to diazepam or MK-801 protected against the respiratory depression. Scopolamine and atropine showed a dose- and time-dependent effectiveness; the longer the seizure progressed the higher the dose of drug required to terminate the seizure, with eventual loss of anticonvulsant activity if the seizure had progressed for 40 min. In contrast, benactyzine and trihexyphenidyl showed a third profile of activity: There was a smaller increase in drug dosage required for anticonvulsant activity as seizure duration increased, and both drugs could terminate seizures that had progressed for 40 min. The early anticonvulsant action of anticholinergics is interpreted as a specific effect that blocks the primary cholinergic excitatory drive that initiates, and first maintains, nerve agent seizures. If allowed to progress, the seizure activity itself recruits excitatory neurotransmitter systems (i.e., NMDA) that eventually maintain the seizure independent of the initial cholinergic drive. This is indicated by the eventual ineffectiveness of scopolamine and atropine as the duration of the seizure progresses. Diazepam and MK-801 appear to act to moderate nerve agent seizures by enhancing inhibitory activity (diazepam) or dampening the secondarily activated noncholinergic excitatory system (MK-801). Benactyzine and trihexyphenidyl represent compounds that possibly have both anticholinergic and NMDA antagonistic properties.
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PMID:Pharmacological modulation of soman-induced seizures. 851 3

The muscarinic antagonist scopolamine blocks conditioned taste aversion (CTA) when microinjected bilaterally into the rat insular cortex shortly before the exposure of the rat to a novel taste (the conditioned stimulus, CS) in CTA training. Scopolamine has no effect when microinjected shortly after the exposure to the novel taste or shortly before the application of the malaise-inducing agent (unconditioned stimulus, UCS). Scopolamine does not affect sensory, motor and retrieval mechanisms required for performing the CTA task, and does not block CTA when injected into another cortical area. The effect of scopolamine is independent of the taste used as CS. Furthermore, microinjection of scopolamine into the insular cortex shortly before the pre-exposure to a new taste in a latent inhibition paradigm, impairs the attenuation of CTA by that pre-exposure. Other muscarinic antagonists, pirenzepine and AF DX-116, have an effect similar to that of scopolamine. Comparison of the dose-dependency curves of the muscarinic antagonists suggests a predominant role in CTA for M2 subtype receptors. Carbachol, a muscarinic agonist, also impairs the encoding of taste in the insular cortex, but the results are confounded by the ability of that ligand to induce seizures. Our findings suggest that cholinergic neuromodulation participates in processing the CS in the gustatory cortex in CTA, either by encoding novelty at the cellular level, or by instructing the neural circuits to store the novel taste representation.
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PMID:Transient impairment of cholinergic function in the rat insular cortex disrupts the encoding of taste in conditioned taste aversion. 888 17

1. The authors examined the anticonvulsant effects of MK-801 on the pilocarpine-induced seizure model. Intraperitoneal injection of pilocarpine (400 mg/kg) induced tonic and clonic seizure. Scopolamine (10 mg/kg) and pentobarbital (5 mg/kg) prevented development of pilocarpine-induced behavioral seizure but MK-801 (0.5 mg/kg) did not. 2. An electrical seizure measured with hippocampal EEG appeared in the pilocarpine-treated group. Scopolamine and pentobarbital blocked the pilocarpine-induced electrographic seizure, MK-801 treatment augmented the electrographic seizure induced by pilocarpine. 3. Brain damage was assessed by examining the hippocampus microscopically. Pilocarpine produced neuronal death in the hippocampus, which showed pyknotic changes. Pentobarbital, scopolamine and MK-801 protected the brain damage by pilocarpine, though in the MK-801-treated group, the pyramidal cells of hippocampus appeared darker than normal. In all treatments, granule cells of the dentate gyrus were not affected. 4. These results indicate that status epilepticus induced by pilocarpine is initiated by cholinergic overstimulation and propagated by glutamatergic transmission, the elevation of which may cause brain damage through an excitatory NMDA receptor-mediated mechanism.
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PMID:MK-801 augments pilocarpine-induced electrographic seizure but protects against brain damage in rats. 906 77


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