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Biomedical subjects

Z Kleinrok

Publications and source records attributed to Z Kleinrok.

At least 181 records · Page 10Linked to original sources
PubMed1985

Injections of picrotoxin and bicuculline into the amygdaloid complex of the rat: an electroencephalographic, behavioural and morphological analysis.

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)

Amygdala↗
PubMed1984

Effects of excitatory amino-acid antagonists on the anticonvulsant action of phenobarbital or diphenylhydantoin in mice.

The effects of L-glutamic acid diethyl ester (GDEE), D,L-alpha-aminoadipic acid (alpha-AA) and D,L-2-aminophosphonovaleric acid (APV) on the anticonvulsant action of phenobarbital and of diphenylhydantoin were studied in mice against electroconvulsions. Anticonvulsants were administered intraperitoneally 60 min and amino-acid antagonists 30 min before the test, by the same route. Neither GDEE (up to 400 mg/kg) nor alpha-AA (up to 100 mg/kg) were found to affect the seizure threshold whilst APV (100 and 200 mg/kg) raised the threshold moderately from 6.2 to 8.4 and 9.0 mA. APV and alpha-AA (up to 100 mg/kg) and GDEE (up to 400 mg/kg) did not affect the anticonvulsant potency of diphenylhydantoin. Only APV in the dose of 200 mg/kg potentiated the protective efficacy of this antiepileptic against maximal electroshock to a relatively low degree. The anticonvulsant action of phenobarbital was enhanced by APV (25-200 mg/kg) and alpha-AA in the dose of 50 but not in the dose of 100 mg/kg, GDEE being completely ineffective. These results suggest that the blockade of N-methyl-D-aspartic acid receptors by alpha-AA and APV is mainly responsible for the potentiation of the anticonvulsant activity of phenobarbital. The anticonvulsant effects of both antiepileptics do not seem to be related to the suppression by GDEE of events mediated by receptors for quisqualic acid.

2-Amino-5-phosphonovalerate↗
PubMed1984

Differential effects of baclofen, gamma-hydroxybutyric acid and muscimol on the protective action of phenobarbital and diphenylhydantoin against maximal electroshock-induced seizures in mice.

This study was designed to compare the effects of baclofen (a GABAB agonist), muscimol (a GABAA agonist) and gamma-hydroxybutyric acid on the protective action of phenobarbital (PB) and diphenylhydantoin (DPH) against electroshock-induced convulsions. All drugs were given intraperitoneally, muscimol being also injected intraventricularly in a dose of 50 ng per mouse. It was found that both baclofen and gamma-hydroxybutyric acid potentiated the anticonvulsant activity of phenobarbital, being ineffective regarding the action of diphenylhydantoin. Conversely, muscimol injected by two different routes moderately enhanced the efficacy of diphenylhydantoin but remained without a significant effect upon the action of phenobarbital.

Animals↗
PubMed1984

Studies on the mechanism of wet dog shakes produced by carbachol in rats.

In an attempt to elucidate the mechanism of wet dog shakes (WDS) produced by carbachol administered into the rat lateral brain ventricle, the effects of blockade of muscarinic and nicotinic receptors on shaking response and the effects of carbachol on central catecholaminergic, serotonergic (5-HT) and GABAergic functions were studied in rats. The muscarinic receptor antagonists, atropine and scopolamine attenuated WDS produced by carbachol, whilst a peripherally active muscarinic receptor antagonist, scopolamine methyl nitrate, failed to influence WDS. The nicotine antagonist, mecamylamine, did not affect WDS caused by carbachol either. Carbachol dose dependently decreased brain concentration of noradrenaline (NA) but failed to affect the concentration of dopamine (DA). While the brain concentration of 5-HT was unchanged, the concentration of 5-hydroxyindoleacetic acid (5-HIAA) was increased in a dose-related manner. The catecholamine turnover times were unaffected whereas 5-HT turnover time was significantly prolonged. Atropine, but not mecamylamine, prevented the decrease in brain NA induced by carbachol. Consequently, the carbachol-induced enhancement in the level of 5-HIAA was completely blocked by atropine and only slightly influenced by mecamylamine. Neither brain GABA concentration nor glutamic acid decarboxylase activity were affected by carbachol. Behavioral and biochemical data suggest that WDS produced by carbachol may be mediated through the stimulation of central muscarinic receptors. The anatomical localization and exact mechanism of carbachol-induced WDS remain to be elucidated.

Animals↗
PubMed1983

Cholinomimetics produce seizures and brain damage in rats.

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.

Amygdala↗
PubMed1983

Does morphine withdrawal produce brain damage in rats?

Behavioral and neuropathological studies of morphine withdrawal in rats made dependent on the narcotic and precipitated with intracerebral and systemic naloxone or withholding the drug were performed. Unilateral injection of naloxone hydrochloride in the dose of 10 micrograms into the amygdaloid complex elicited severe withdrawal signs including jumping, wet dog shakes, paw tremor, diarrhoea and gustatory automatisms whereas microinjections of naloxone (10 micrograms) into the dorsal hippocampus resulted in severely less pronounced withdrawal behaviors. Histological examination of frontal forebrain sections by light microscopy did not reveal any neuropathological alterations within the brains of rats either dependent on morphine or in those in which morphine withdrawal was precipitated with naloxone or by abrupt termination of morphine intake. The negative finding of the present study does not necessarily mean that there is no relationship between morphine withdrawal and brain damage.

Animals↗
PubMed1983

Intraamygdaloid morphine produces seizures and brain damage in rats.

Behavioral and neuropathological responses to increasing doses of morphine hydrochloride (10-75 micrograms) administered into the rat amygdala were studied. Unilateral microinjections of morphine in doses of 40 and 75 micrograms produced a sequence of behavioral alterations including staring spells, gustatory automatisms, wet dog shakes, motor limbic seizures and limbic status epilepticus. Lower doses of morphine (10 and 20 micrograms) showed different threshold for these behavioral phenomena but a similar time course of development. Histological examination of frontal forebrain sections revealed widespread, apparently seizure-mediated pattern of brain damage. Neuropathological alterations were observed in the olfactory cortex, thalamus, neocortex, hippocampal formation and amygdaloid complex. Pretreatment of animals with diazepam (10 mg/kg i.p.) prevented the development of sustained limbic seizures and brain damage caused by morphine, while pretreatment with naloxone hydrochloride (2-20 mg/kg i.p.) failed to affect morphine-induced convulsant activity and brain damage. These results may suggest that morphine elaborates sustained limbic seizures and widespread brain damage by mechanism underlying the antagonism of inhibitory amino acid neurotransmission and opioid receptors do not seem to be involved.

Amygdala↗
PubMed1983

Intrahippocampal bethanechol in rats: behavioural, electroencephalographic and neuropathological correlates.

Unilateral microinjections of bethanechol chloride into the CA3 subfield of the dorsal hippocampus in unrestrained rats produced a seizure-related type behavioural and disseminated brain damage syndrome. Injection of bethanechol in the dose of 50 micrograms resulted in locomotor activation, mouth movements, teeth chattering, chewing, wet dog shakes and mild limbic seizures. Shortly after intrahippocampal injection the electroencephalogram (EEG) showed an increase in the frequency of the theta rhythm in both hippocampi. Then EEG showed spiking activity of high frequency in the injected hippocampus, with rapid propagation to the lateral septum, amygdala, neocortex and contralateral hippocampus. The periods of spiking activity of high frequency were followed by depression in the background EEG rhythm with some interspersed spike and wave complexes of very low frequency. Histological examination of frontal forebrain sections revealed disseminated, apparently seizure-mediated pattern of brain damage. The patterning of distant damage after intrahippocampal injections of bethanechol involved the piriform cortex, entorhinal cortex, olfactory tubercle, anterior olfactory nucleus, subiculum, amygdaloid complex, temporoparietal cortex and hypothalamic nuclei. Neuropathological alterations were occasionally observed in the lateral septum and thalamus. These results seem to establish a causative relationship between excessive stimulation of cholinergic muscarinic receptors in the hippocampal formation and epileptic brain damage.

Acetylcholine↗
PubMed1983

Limbic seizures produced by pilocarpine in rats: behavioural, electroencephalographic and neuropathological study.

Behavioural, electroencephalographic and neuropathological responses to increasing doses of pilocarpine (100-400 mg/kg) administered intraperitoneally to rats were studied. At the dose of 400 mg/kg pilocarpine produced a sequence of behavioural alterations including staring spells, olfactory and gustatory automatisms and motor limbic seizures that developed over 1-2 h and built up progressively into limbic status epilepticus. Smaller doses showed different threshold for these behavioural phenomena but a similar time course of development. The earliest electrographic alterations occurred in the hippocampus and then epileptiform activity propagated to amygdala and cortex. Subsequently electrographic seizures appeared in both limbic and cortical leads. The ictal periods recurred each 5-15 min and were followed by variable periods of depression of the electrographic activity. The sequence of electrographic changes correlated well with the development of behavioural phenomena. Histological examination of frontal forebrain sections revealed disseminated, apparently seizure-mediated pattern of brain damage. Neuropathological alterations were observed in the olfactory cortex, amygdaloid complex, thalamus, neocortex, hippocampal formation and substantia nigra. Pretreatment of animals with scopolamine (20 mg/kg) and diazepam (10 mg/kg) prevented the development of convulsive activity and brain damage. These results show that systemic pilocarpine in rats selectively elaborates epileptiform activity in the limbic structures accompanied by motor limbic seizures, limbic status epilepticus and widespread brain damage. It is suggested that a causative relationship between excessive stimulation of cholinergic receptors in the brain and epileptic brain damage may exist.

Animals↗