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Biomedical subjects

L Turski

Publications and source records attributed to L Turski.

At least 127 records · Page 7Linked to original sources
PubMed1983

Reversal of the muscle relaxant effect of diazepam but not of progabide by a specific benzodiazepine antagonist: Ro 15-1788.

The muscle relaxant effects of diazepam and progabide were studied in mutant Han-Wistar rats which exhibit spontaneous tonic activity in the electromyogram of the gastrocnemius-soleus muscle. Treatment with diazepam or progabide produced a dose-related reduction of the spontaneous activity measured in the electromyogram. The depressant effect of diazepam, but not that of progabide was antagonized by the specific benzodiazepine antagonist Ro 15-1788. From these data it is apparent that the muscle relaxant effect of progabide is not mediated through an alteration of benzodiazepine receptors.

Animals↗
PubMed1983

Is the muscle relaxant effect of diazepam in spastic mutant rats mediated through GABA-independent benzodiazepine receptors?

Diazepam (0.4-0.8 mg/kg i.p.) reduced the spontaneous activity in the electromyogram (EMG) recorded from the gastrocnemius-soleus muscle of spastic mutant Han--Wistar rats in a dose-dependent manner. The depressant effect of diazepam (0.8 mg/kg) on the EMG activity was antagonized by Ro 15-1788 (5 mg/kg i.p.) and by picrotoxin (2 mg/kg i.p.), but not by bicuculline (2 mg/kg i.p.). These results suggest that diazepam depresses EMG activity of mutant rats by mechanisms related to the interaction of the drug with GABA-independent benzodiazepine receptors.

Animals↗
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

Reversal of the muscle relaxant effect of diazepam by the specific benzodiazepine antagonist Ro 15-1788: an electromyographic study in morphine model of muscular rigidity in rats.

The effects of the benzodiazepines diazepam and midazolam on the rigidity produced by systemic administration of morphine (15 mg/kg i.p.) were studied in rats. The rigidity was recorded as a tonic activity from the gastrocnemius-soleus muscle of non-anesthetized rats in the electromyogram. Both diazepam (1-5 mg/kg i.p.) and midazolam (2.5 and 5 mg/kg i.p.), when administered 45 min after morphine, temporarily antagonized the muscular rigidity. When the competitive antagonist Ro 15-1788 (ethyl-8-fluoro-5, 6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5a]-[1,4]benzodiazepine-3 -carboxylate) (5 mg/kg i.p.) was administered together with diazepam (5 mg/kg i.p.), it prevented the effect of diazepam, although by itself it did not affect the morphine-induced muscular rigidity. Our results suggest that diazepam, by acting on benzodiazepine receptors, can antagonize the morphine-induced muscular rigidity. The latter phenomenon might serve as a model for some types of muscular rigidity observed in humans.

Animals↗
PubMed1983

The role of the substantia nigra in motility of the rat. Muscular rigidity, body asymmetry and catalepsy after injection of morphine into the nigra.

Unilateral injection of morphine (1.0, 2.5 or 5.0 micrograms/0.5 microliter) into the substantia nigra pars reticulata produced, in a dose-dependent way, tonic activity in the electromyogram (EMG) recorded from the ipsilateral gastrocnemius-soleus muscle of unanaesthetized rats. The effect produced by 5 micrograms of morphine was antagonized by co-administration of 5 micrograms of naloxone. Bilateral injection of morphine (5 micrograms each side) also produced a tonic activity in the EMG and catalepsy, but no asymmetry of posture. Unilateral injection of morphine (5 micrograms) into the substantia nigra pars compacta produced contralateral turning and/or stereotypy, but no tonic activity in the EMG. Naloxone (5 micrograms), when injected into the substantia nigra failed to produce any tonic activity in the EMG or any catalepsy. Larger doses of naloxone (10 or 20 micrograms) produced slight to moderate tonic activity in the EMG when injected into the pars reticulata. Injections of saline (0.5 microliter) into either the reticulata or compacta were ineffective. Bilateral lesions of the caudate nucleus with kainic acid (1 microgram each side) did not prevent the development either of the tonic activity in the EMG or of the catalepsy, which were both produced by unilateral injection of morphine (5 micrograms) into the pars reticulata. These results suggest that opioid mechanisms in the nigra might play a role in the regulation of posture and muscle tone and participate in the expression of motor functions controlled by the striatum (and probably also by the nucleus accumbens).

Animals↗
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↗
PubMed1982

Role of GABAergic mechanisms in the substantia nigra pars reticulata in modulating morphine-induced muscular rigidity in rats.

Systemic administration of morphine (15 mg/kg i.p.) induced a muscular rigidity in rats, which was recorded from the gastrocnemius-soleus muscle as tonic activity in the electromyogram (EMG). Administration of muscimol (12.5 or 25 ng) into the substantia nigra pars reticulata (SNR) antagonized the rigidity in a dose-dependent manner, whereas bicuculline enhanced it. It was concluded that GABAergic mechanisms in the SNR play an important role in mediating or modulating the expression of the morphine-induced rigidity, which is known to be due to an alteration of striatal function via opioid receptors located in this brain area.

Animals↗
PubMed1982

Dyphenylhydantoin enhancement of diazepam effects on locomotor activity in mice.

The interaction of diazepam and diphenylhydantoin on locomotor activity and rearing behavior was studied in mice. Pretreatment of mice with diphenylhydantoin (4.0 and 8.0 mg/kg) significantly reversed the stimulatory effects of low doses of diazepam and considerably increased the depressant effects of the benzodiazepine on locomotor activity and rearing. Neither diazepam (up to 4.0 mg/kg), diphenylhydantoin (8.0 mg/kg) alone, nor combined treatment with both drugs affected brain GABA level and glutamic acid decarboxylase (GAD) activity at any dosage used. The present behavioral and biochemical data suggests that some of the pharmacological effects of diazepam need not be related to GABAergic mechanisms.

Animals↗
PubMed1982

Interaction between phenytoin and diazepam in mutant Han-Wistar rats with progressive spastic paresis.

The muscle relaxant (antispastic) effect of diazepam, alone or in combination with phenytoin, was studied in mutant Han-Wistar rats with progressive spastic paresis. Alone, phenytoin did not alter the spontaneous activity in the electromyogram (EMG) of the gastrocnemius soleus (GS) muscle of mutant rats, but strongly enhanced the depressant action of diazepam on the spontaneous EMG activity. Picrotoxin reduced the antispastic effect of diazepam alone and partially reversed the antispastic effect of combined treatment. Therefore, the antagonistic effect of picrotoxin on the reduction of the spontaneous activity in the EMG produced by the combination of both drugs hardly suggests an interaction of picrotoxin with phenytoin, but rather indicates an interaction with the effect of diazepam. Phenytoin enhancement of the depressant action of diazepam on the spontaneous EMG activity of mutant rats strongly suggests the potential therapeutic usefulness of the combined treatment with both drugs.

Animals↗
PubMed1982

Effects of combined treatment with diphenylhydantoin and different benzodiazepines on pentylenetetrazol- and bicuculline-induced seizures in mice.

The anticonvulsant effects of clonazepam, nitrazepam and chlordiazepoxide alone, or combined with diphenylhydantoin, were studied on pentylenetetrazol- and bicuculline-induced seizures. Diphenylhydantoin remained without influence upon the chemically induced convulsions but potentiated the antipentylenetetrazol activity of clonazepam and nitrazepam. Also, the combination of diphenylhydantoin and clonazepam resulted in a distinct decrease in the ED50 value of the latter drug against the tonic (but not the clonic) phase of bicuculline-induced seizures. On the other hand, diphenylhydantoin did not enhance the anticonvulsant activity of chlordiazepoxide against both convulsants used nor did it affect the protective action of nitrazepam against bicuculline. The suggestion is made that a diphenylhydantoin-induced increase in the total number of specific benzodiazepine receptors might be of importance for the potentiation of the antipentylenetetrazol effects of some benzodiazepines. The interaction between diphenylhydantoin and clonazepam seems to be more complex and probably involves other mechanisms.

Animals↗
PubMed1982

On the possible role of excitatory amino acids in the striatum in mediating morphine-induced muscular rigidity.

The possible role of excitatory amino acids in the striatum in mediating tonic activity in the electromyogram (EMG) was studied. Glutamate diethylester (GDEE) (100-400 nmoles) induced a tonic activity in the EMG in a dose-dependent way when injected into the striatum. This effect was well antagonized by intrastriatal injection of quisqualic acid (5 and 25 nmoles), less by kainic acid (5 nmoles) and not significantly by N-methyl-D-aspartate (NMDA) (30 nmoles). Systemic administration of naloxone (2 mg/kg IP) did not inhibit the GDEE-induced activity in the EMG. The tonic activity in the EMG, induced by systemic administration of morphine (15 mg/kg IP) was not significantly influenced by injection of GDEE (200 nmoles) into the striatum, but was first decreased and then slightly enhanced by intrastriatal injection of quisqualic acid (25 and 50 nmoles), not affected by kainic acid (5 nmoles) and first slightly decreased and then strongly enhanced by NMDA (15 and 30 nmoles). Injection of kainic acid (5 nmoles), quisqualic acid (5 or 25 nmoles) or NMDA (30 nmoles) alone into the striatum did not produce any tonic activity in the EMG. Our results support the assumption that quisqualic acid, kainic acid and NMDA react with different types of receptors for excitatory amino acids in the striatum. Both quisqualicacid and NMDA showed a biphasic action, whereas kainic acid was ineffective. Furthermore, the activity in the EMG induced by morphine might be at least partly due to a functional antagonism of morphine against glutamate in striatal neurons.

Amino Acids↗
PubMed1982

Evidence that opioid receptors in the substantia nigra pars reticulata are relevant in regulating the function of striatal efferent pathways.

A tonic activity in the electromyogram (EMG) was induced in conscious rats by injections of morphine either systemically or into the caudate nucleus. This activity was antagonized by injections of naloxone into the substantia nigra pars reticulata. These findings suggest that opioid receptors in this brain area are relevant in regulating the function of striatal efferent pathways.

Animals↗
PubMed1982

Anticonvulsant action of phenobarbital, diazepam, carbamazepine, and diphenylhydantoin in the electroshock test in mice after lesion of hippocampal pyramidal cells with intracerebroventricular kainic acid.

The electroshock test-taking hind limb tonic extension as the end point-was carried out on the fifth day after the intracerebroventricular injections of kainic acid (KA; 0.2 microgram per mouse). The following antiepileptics were tested for the anticonvulsant effects both in naive and KA-lesioned mice: phenobarbital (20 mg/kg), diazepam (8 mg/kg), carbamazepine (15 mg/kg) and diphenylhydantoin (10 mg/kg), all drugs being injected intraperitoneally 60 min before electroconvulsions. It was found that the protective effects of phenobarbital and diazepam were distinctly reduced in KA-lesioned animals when compared to naive mice. However, both carbamazepine and diphenylhydantoin protected KA-injected and control animals to a similar degree. Further, intracerebroventricular injections of KA resulted in the substantial loss of pyramidal cells in the whole CA3 field of the hippocampus. It is suggested that the intact hippocampus is necessary for the development of the full anticonvulsant effects of phenobarbital and diazepam, whilst the site of action of carbamazepine and diphenylhydantoin is independent of the hippocampus.

Animals↗
PubMed1982

Induction of wet dog shakes by intracerebroventricular bethanechol in rats. Antagonism by neurotransmitter receptor blockers.

Bethanechol chloride, administered intracerebroventricularly, induces a characteristic wet dog shake (WDS) response in rats in a dose-related manner. WDS induced by bethanechol at the dose of 100 micrograms was antagonized by atropine, scopolamine and spiperone (muscarinic cholinergic and dopaminergic antagonists, respectively), whilst metergoline, methysergide, phentolamine, propranolol and bicuculline (serotonergic, alpha-adrenergic, beta-adrenergic and GABA-ergic antagonists) fail to inhibit this effect. The present experiments show that the shaking response may be produced by bethanechol, a potent muscarinic agent administered by the intracerebral route, and suggest that bethanechol-induced shaking behavior in rats may be a useful animal model for delineating agents with antimuscarinic activity.

Animals↗
PubMed1982

The involvement of catecholaminergic mechanisms in the appearance of wet dog shakes produced by carbachol chloride in rats.

Noradrenaline (NA), methoxamine, dopamine (DA), given intracerebroventricularly (ICV), and L-DOPA, administered systemically, significantly blocked wet dog shakes (WDS) produced by carbachol chloride (10 microgram/10 microliter, ICV) in rats. Reserpine, alpha-methyl-p-tyrosine and FLA 63 did not affect WDS, while diethyldithiocarbamic acid depressed it. Aceperone and yohimbine weakened shaking response to carbachol but phentolamine given ICV showed no effect on WDS. Propranolol and isoproterenol administered ICV did not significantly influence WDS. Apomorphine failed to affect WDS induced by carbachol. Pimozide and spiperone were also ineffective against WDS, but amphetamine and metoclopramide efficiently blocked it. Selective depletion of brain NA concentration considerably enhanced WDS, while selective depletion of brain DA concentration failed to affect it. These results suggest that carbachol-induced WDS behavior is under the inhibitory control of noradrenergic neurons.

Animals↗