Biomedical subjects

L Turski

Publications and source records attributed to L Turski.

At least 109 records · Page 6Linked to original sources

PubMed1985

Rigidity and catalepsy after injections of muscimol into the ventromedial thalamic nucleus: an electromyographic study in the rat.

The cataleptic state induced by injection of the GABAmimetic drug muscimol into the rat's ventromedial thalamic nucleus (VM) was examined using an electromyographic (EMG) approach. Muscimol in doses up to 50 ng/0.5 microliter injected into the VM induced a tonic EMG activity in the gastrocnemius muscle which is considered to be a measure of limb rigidity. This tonic EMG activity was found to be dose-dependent, GABA specific and locus specific. By recording EMG signals from chronically implanted electrodes in awake, unrestrained rats it was shown that muscular reactions serving to maintain the animal's static equilibrium were intact in the state of VM induced catalepsy. However, animals were unable to initiate movements or locomotion even when they were forced by strong external stimuli. It was found that the animals' immobility was due to an inability to induce a phasic activation of their muscles whereas tonic activation still occurred. It is concluded that the rat's VM is part of a neuronal chain conducting information relevant for the expression of limb rigidity, the VM is involved in the central mechanisms responsible for the phasic activation of a set of muscles.

Animals↗

PubMed1985

Modification of the anticonvulsant activity of 2-amino-5-phosphonovalerate by agents affecting different neurotransmitter systems.

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.

2-Amino-5-phosphonovalerate↗

PubMed1985

Effects of morphine and naloxone on pilocarpine-induced convulsions in rats.

Systemic administration of morphine hydrochloride (MF; 5-80 mg/kg; i.p.) in rats enhanced the epileptogenic potential of pilocarpine hydrochloride (PIL) in a dose-dependent manner. PIL, 100 mg/kg; i.p., which did not result in convulsions by itself, produced sustained limbic seizures and epileptic brain damage in MF-pretreated rats. MF-induced enhancement of PIL neurotoxicity was blocked by naloxone hydrochloride (NAL; 2 and 10 mg/kg; i.p.). Administration of NAL (2-20 mg/kg) prior to PIL in the dose of 380 mg/kg moderately decreased the incidence of convulsions, brain damage and lethal toxicity produced by this agent. These results support the hypothesis that opiate mechanisms are involved in the maintenance of the threshold for propagation of seizure activity within limbic circuits.

Animals↗

PubMed1985

Phosphonic analogues of excitatory amino acids raise the threshold for maximal electroconvulsions in mice.

2-Amino-5-phosphonopentanoic acid (100 and 200 mg/kg) and 2-amino-7-phosphonoheptanoic acid (50-200 mg/kg i.p.) significantly elevated the threshold for maximal electroconvulsions in mice, the latter being more effective in this respect. In contrast, neither alpha-aminoadipic acid nor L-glutamic acid diethyl ester (up to 200 and 400 mg/kg, respectively) offered any protection. The present results add further evidence to support the importance of the blockade of N-methyl-D-aspartic acid receptor-mediated events in the suppression of seizure activity.

2-Amino-5-phosphonovalerate↗

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↗

PubMed1985

Evaluation of the muscle relaxant properties of a novel beta-carboline, ZK 93423 in rats and cats.

The muscle relaxant action of ZK 93423 (6-benzyloxy-4-methoxymethyl-beta-carboline-3-carboxylate ethyl ester), a novel beta-carboline with agonistic properties at the benzodiazepine receptor, was examined by assessing its effect on the tonic electromyogram (EMG) activity of the gastrocnemiussoleus (GS) muscle of genetically spastic rats and on ventral root reflexes, presynaptic inhibition and fusimotor activity in the spinal cord of decerebrate cats. ZK 93423 (0.1-10.0 mg kg-1) depressed the tonic EMG activity in mutant rats in a dose-dependent manner. This effect was reversed by the benzodiazepine antagonist Ro 15-1788 (5.0 mg kg-1). Both ZK 93423 (0.5 mg kg-1) and diazepam (0.3 mg kg-1) enhanced the presynaptic inhibition of the GS muscle and associated dorsal root potentials in decerebrate cats in an almost identical manner. The actions of both drugs were reversed by Ro 15-1788 (5.0 mg kg-1). ZK 93423 (0.5 mg kg-1) and diazepam (0.3 mg kg-1) depressed the activity of both static and dynamic fusimotor neurones, as deduced from changes in the afferent responses of muscle spindle primary endings to low frequency (1 s-1) sinusoidal stretching. The depressant action of diazepam (0.3 mg kg-1) was weaker than that of ZK 93423 (0.5 mg kg-1). The actions of both drugs were reversed by Ro 15-1788 (5.0 mg kg-1). ZK 93423 (0.5 mg kg-1) failed to alter the magnitude of monosynaptic ventral root reflexes evoked by electrical stimulation of a flexor and an extensor nerve, whereas diazepam (0.3 mg kg-1) had a depressant effect on both types of monosynaptic reflexes, which was antagonized by Ro 15-1788 (5.0 mg kg-1). Neither ZK 93423 (0.5 mg kg-1) nor diazepam (0.3 mg kg-1) depressed polysynaptic ventral root reflexes evoked by electrical stimulation of a flexor and a cutaneous nerve. The present results demonstrate that ZK 93423 exerts a potent muscle relaxant action due to a specific interaction with benzodiazepine receptors. However, its profile of actions on spinal motor mechanisms is not identical to that of diazepam.

Animals↗

PubMed1985

Effects of 2-chloroadenosine on amygdaloid and hippocampal kindled seizures.

The effects of 2-chloroadenosine (2-CLA), a metabolically stable analogue of adenosine, on amygdaloid and hippocampal kindled seizures were examined in rats. Intraperitoneal injections of 2-CLA, 1.0 mg/kg, did not modify the evolution of either amygdaloid or hippocampal kindled seizures. 2-CLA in the dose of 3.0 mg/kg shortened the duration of both behavioral and electrographic convulsive manifestations while the dose of 5.0 mg/kg completely blocked the evolution of the kindled seizures. The results indicate that purinergic mechanisms are involved in the maintenance and modulation of the seizure threshold within the limbic system.

2-Chloroadenosine↗

PubMed1984

GABAergic mechanisms in mediating muscular rigidity, catalepsy and postural asymmetry in rats: differences between dorsal and ventral striatum.

In rats, the GABAergic agonist muscimol was injected unilaterally either into the mid ventroposterior striatum (ventral striatum) or into the mid dorsoposterior striatum (dorsal striatum), and the following parameters were estimated: (1) a tonic activity in the electromyogram (EMG) recorded from the gastrocnemius-soleus (GS) muscle, which appears to reflect a muscular rigidity; (2) catalepsy, and (3) asymmetries in posture. Injection of muscimol (25 or 50 ng) into the ventral striatum produced tonic EMG activity, catalepsy and ipsiversive posture; these signs were much less pronounced or not observed after injections into the dorsal striatum. Co-administration of bicuculline (500 ng) into the ventral striatum, or simultaneous injection of muscimol (25 ng) into the substantia nigra pars reticulata (SNR), antagonized both the tonic EMG activity and the catalepsy produced by injection of 50 ng muscimol into the ventral striatum. These results seem to support the assumption that all 3 symptoms mentioned can be produced by an inhibition of striatonigral GABAergic neurones. These symptoms are probably due to a disinhibition of nigrofugal neurones, originating in the SNR.

Animals↗

PubMed1984

Seizures produced by pilocarpine in mice: a behavioral, electroencephalographic and morphological analysis.

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.

Animals↗

PubMed1984

CGS 8216, Ro 15-1788 and methyl-beta-carboline-3-carboxylate, but not EMD 41717 antagonize the muscle relaxant effect of diazepam in genetically spastic rats.

Diazepam (0.4-4 mg/kg i.p.) reduced the spontaneous tonic activity in the electromyogram (EMG) recorded from the gastrocnemius-soleus muscle of spastic mutant Han-Wistar rats in a dose-dependent manner. The muscle relaxant effect of diazepam was antagonized by the benzodiazepine antagonists Ro 15-1788 (5 mg/kg i.p.), beta-CCM (2 mg/kg i.p.) and CGS 8216 (5 mg/kg i.p.), but not by EMD 41717 (50 mg/kg i.p.). These results add further support to the hypothesis that Ro 15-1788, CGS 8216 and beta-CCM do antagonize all pharmacological effects of benzodiazepines while EMD 41717 displays more selectivity in antagonizing the different actions of benzodiazepines.

Animals↗

PubMed1984

Effect of aminophylline on muscle relaxant action of diazepam and phenobarbitone in genetically spastic rats: further evidence for a purinergic mechanism in the action of diazepam.

The effect of aminophylline on the muscle relaxant action of both diazepam and phenobarbitone was studied in genetically spastic rats of the Han-Wistar strain which exhibit spontaneous tonic activity in the electromyogram of the gastrocnemius-soleus muscle. Both diazepam (0.8 and 4.0 mg/kg i.p.) and phenobarbitone (20 and 30 mg/kg i.p.) reduced the spontaneous activity measured in the electromyogram in a dose-related manner. Aminophylline (50 mg/kg i.p.), a methylxanthine with potent antagonistic activity of adenosine-mediated inhibition, partially reversed the muscle relaxant action of diazepam (4 mg/kg) but not that produced by phenobarbitone. The muscle relaxant effect of phenobarbitone (30 mg/kg) was antagonised by beta-carboline-3-carboxylic acid methylester (beta-CCM), 2 mg/kg i.p. The reversal of the muscle relaxant effect of phenobarbitone produced by beta-CCM was abolished by CGS 8216 (2-phenylpyrazolo-(4,3c)quinolin-3(5H)-one), 5 mg/kg i.p. Aminophylline altered neither the muscle relaxant effect of a low dose of diazepam (0.8 mg/kg) nor the reversal of the muscle relaxant effect of phenobarbitone produced by beta-CCM. These findings indicate that the interaction between diazepam and aminophylline does not involve competition for the benzodiazepine receptor and add further support to the suggestion that purinergic mechanisms may be engaged in the muscle relaxant action of diazepam.

Aminophylline↗

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

A specific benzodiazepine antagonist CGS 8216 reverses the muscle relaxant effect of diazepam but not that of phenobarbitone.

The muscle relaxant effects of diazepam and phenobarbitone were studied in mutant Han-Wistar rats which exhibit spontaneous tonic activity in the electromyogram of the gastrocnemius-soleus muscle. Diazepam and phenobarbitone significantly and dose- relatedly reduced the spontaneous activity measured in the electromyogram. The benzodiazepine receptor antagonist CGS 8216 reversed the depressant effect of diazepam but not that produced by phenobarbitone. The results add further support to the suggestion that CGS 8216 may be useful to investigate the effects modified by benzodiazepine receptors in vivo.

Animals↗

PubMed1984

Role of muscarinic cholinergic mechanisms in the substantia nigra pars reticulata in mediating muscular rigidity in rats.

Bethanechol chloride (5-25 micrograms), when injected into the substantia nigra pars reticulata (SNR) of rats, produced muscular rigidity in a dose-dependent way, and in addition, catalepsy and ipsilateral posture. The effects of bethanechol in the dose of 25 micrograms were prevented by co-administration of 10 micrograms scopolamine hydrochloride. Injections of 25 micrograms bethanechol or 10 micrograms scopolamine into the reticulata only slightly affected the muscular rigidity produced by 15 mg/kg i.p. morphine hydrochloride. The results suggest that muscarinic cholinergic mechanisms in the substantia nigra pars reticulata, although effective by themselves, affect by expression of at least one striatal functional alteration, the muscular rigidity, in a less effective way than GABAergic or endogenous opioid mechanisms do.

Animals↗

PubMed1984

Stereotypy, locomotor and cataleptic effects produced by drugs influencing dopaminergic systems in a mutant strain of Wistar rats: a genuine model of basal ganglia dysfunction?

The mutant strain of Wistar rats carrying an autosomal recessive gene defect is characterized by a sequence of progressively developing behavioural alterations including hyperexcitability, tremor, olfactory and gustatory automatisms, bradykinesia, ataxia, rigidity, paresis and cachexia. The stereotypy and locomotor responses to increasing doses of apomorphine hydrochloride and D-amphetamine sulphate, and the catalepsy response to increasing doses of haloperidol were studied in mutant rats at the age of 6-7 weeks. In the mutants, both the stereotypy and locomotor responses to amphetamine were enhanced, while stereotypy and locomotor effects induced by apomorphine were unaltered. The cataleptic response to haloperidol was significantly diminished compared to controls. These findings indicate a derangement in the function of basal ganglia in the mutants.

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

Nigral GABAergic mechanisms and EMG activity in rats: differences between pars reticulata and pars compacta.

The effects of GABAergic drugs, injected unilaterally either into the substantia nigra pars compacta (SNC) or pars reticulata (SNR) of rats, on motility (tonic activity in the gastrocnemius-soleus muscle, turning behaviour, catalepsy) were studied. Administration of the GABAergic antagonist bicuculline (12.5-50 ng) into the SNR produced tonic activity in the EMG, catalepsy and an ipsiversive posture. The tonic EMG activity was prevented by co-administration of muscimol (25 ng), but not by bilateral lesions of the striatum with kainic acid. Tonic activity in the EMG was also produced by injections of muscimol (25 ng) into the SNC, whereas injections into the SNR led to contraversive circling and no tonic activity in the EMG. Because a new parameter was used--the tonic activity in the EMG--our results support the assumption that GABAergic mechanisms in both parts of the substantia nigra play a different role in regulating and mediating striatal function.

Animals↗