Biomedical subjects

K Ossowska

Publications and source records attributed to K Ossowska.

At least 19 recordsLinked to original sources

PubMed1998

Chronic treatment with haloperidol diminishes the phencyclidine-induced sensorimotor gating deficit in rats.

Prepulse inhibition is a model in which a weak subthreshold stimulus (prepulse), presented to an individual before a strong stimulus (pulse), inhibits a startle response to the latter. A deficit of prepulse inhibition induced by dopaminomimetics and antagonists of NMDA receptors has been suggested as an animal model of the sensorimotor deficit in schizophrenia. The aim of the present study was to examine the effect of chronic treatment with the classic neuroleptic haloperidol on the disruption of prepulse inhibition induced by the uncompetitive antagonist of NMDA receptors phencyclidine (PCP, 5 mg/kg sc). Haloperidol in a dose of 1 mg/kg/day was given to rats in drinking water for 3 months. The PCP-induced reduction in prepulse inhibition was not reversed by short-term (4-day) haloperidol administration. In contrast, long-term treatment with haloperidol (6 weeks or 3 months) diminished the PCP-induced effect. The present study suggests that the improvement in sensorimotor gating in the PCP model in rats by prolonged treatment with haloperidol may reflect its antipsychotic action.

Animals↗

PubMed1997

Age-related muscle stiffness: predominance of non-reflex factors.

This study was aimed at assessing the contribution of reflex and non-reflex factors to the muscle tone of old female Wistar rats. The hind foot of a rat was flexed or extended at the ankle joint by 25 degrees over 250 ms. The resistance of the foot to passive movements (torque, mechanomyogram), as well as the reflex electromyographic activity in the gastrocnemius and tibialis anterior muscles, were recorded simultaneously. Moreover, the impact of the blockade of the reflex activity caused by the local anesthetic lignocaine (1-2 ml of a 2% solution, injected in the vicinity of the sciatic nerve) on the muscle tone was investigated. Additionally, old rats' hind leg muscle samples were analysed using fluorescent microscopy for the expression of fibronectin, which is an early marker of connective tissue formation. It has been shown that old rats are characterized by (i) a substantially increased resistance of flexor muscle stiffness (measured during extension) and unchanged resistance of extensors (measured during flexion), (ii) the loss of a major part of the reflex electromyographic activity and (iii) the increased content of fibronectin in muscles. Moreover, it has been shown that lignocaine, which completely blocked the electromyographic reflex activity in the gastrocnemius and tibialis anterior muscles in young animals, was unable to counteract the resistance of these muscles to passive movements in old rats. The present results suggest that the muscle stiffness seen in old rats is not due to a reflex response, but depends mainly on non-reflex factors--chiefly on a large overgrowth of non-elastic connective tissue replacing degenerated active muscle fibers.

Aging↗

PubMed1996

The influence of dizocilpine (MK-801) on the reserpine-enhanced electromyographic stretch reflex in rats.

The electromyographic (EMG) stretch reflex in the gastrocnemius and tibialis anterior muscles was elicited by passive bending and stretching of the rat's hind foot in the ankle joint. The EMG stretch reflex was increased by pretreatment with reserpine (10 mg/kg ip) which is a model compound commonly used to induce parkinsonian rigidity in laboratory animals. Dizocilpine (MK-801) (0.32, 0.64 and 1.28 mg/kg sc) inhibited long-latency supraspinal components of the reserpine-increased EMG stretch reflex, whereas a short-latency spinal component was not diminished. The present results suggest that MK-801 exhibits an antiparkinsonian action against reserpine-induced rigidity.

Animals↗

PubMed1996

Haloperidol-increased muscle tone in rats as a model of parkinsonian rigidity.

The aim of the present study was to find out whether haloperidol-induced rigidity was similar to that seen in parkinsonism. Simultaneous measurements of the muscle resistance (mechanomyogram, MMG) of the hind foot to passive flexion and extension in the ankle joint, as well as determination of the electromyographic (EMG) activity of the gastrocnemius and tibialis anterior muscles of rats were carried out. Haloperidol was injected in doses of 0.5-10 mg/kg 1 h before the start of measurements. Haloperidol increased, in a dose-dependent manner, the muscle resistance of the rat's hind leg to passive movements. Muscle rigidity was accompanied with an increase resting, as well as in the stretch-induced long-latency EMG activity (in which supraspinal reflexes are most probably involved) in both those muscles, whereas the short-latency EMG activity (first large bursts of EMG activity, beginning ca. 9 ms after the start of a movement, probably of a spinal origin) was significantly decreased. The obtained results suggest that the haloperidol-increased MMG/EMG activity might be a good model of parkinsonian rigidity.

Animals↗

PubMed1996

Influence of 6-hydroxydopamine lesion of the dopaminergic nigrostriatal pathway on the muscle tone and electromyographic activity measured during passive movements.

The aim of the present study was to find out whether a 6-hydroxydopamine-induced lesion of the substantia nigra in rats would evoke muscular rigidity of the parkinsonian type. Simultaneous measurements of muscle resistance (mechanomyogram) of the hind foot to passive flexion and extension at the ankle joint, as well as of the electromyographic activity of the antagonistic muscles of the ankle joint--the gastrocnemius and tibialis anterior--in rats were carried out one, two and four weeks after bilateral injections of 6-hydroxydopamine (6.5 micrograms/microliter) into the substantia nigra. After immunohistochemical staining of brain sections for tyrosine hydroxylase, the rats were divided into two groups in which, on average, either 70% (63-80%) or 89% (81-96%) of nigral cells degenerated. Larger lesions increased the resistance (mechanomyogram) of the rat's hind leg to passive movements two weeks after 6-hydroxydopamine injection, whereas smaller lesions did not. Muscle rigidity was accompanied by an increase in the movement-induced reflex electromyographic activity in both muscles, mainly in long-latency components which are most probably influenced by supraspinal mechanisms. However, in spite of relatively large lesions of nigral dopamine cells, already four weeks after the lesion, muscle rigidity and the respective electromyographic activity diminished dramatically, which seems to result from very effective compensatory mechanisms operating in young lesioned rats. The results suggest that the muscle rigidity induced by the 6-hydroxydopamine nigral lesion seems to be a good model of parkinsonian rigidity.

Animals↗

PubMed1996

The role of reflex activity in the regulation of muscle tone in rats.

The aim of the study was to assess the contribution of reflex activity to the regulation of muscle tone in rats. The experiment was carried out on young Wistar male and female rats. The hindfoot of a rat was flexed or extended at the ankle joint by 25 deg over 250 ms. The resistance of the foot to passive movements, as well as the electromyographic (EMG) activity in the gastrocnemius and the tibialis anterior muscles, were recorded simultaneously. During passive movements, reflex EMG activity developed simultaneously in both antagonistic muscles of the foot. Three components were distinguished: a short-latency EMG-A (within the first 0-20 ms of a movement), long-latency EMG-B (within 60-160 ms), and EMG-C (within 220-340 ms). When the amplitudes of EMG-B and EMG-C components of the gastrocnemius muscle reflex response were greater than 50 microV, a significant correlation was found between them and the maximum resistance of the hindfoot (MMGmax) during flexion, whereas no such correlation was observed for the tibialis anterior muscle. No correlation was found when the amplitudes of the log-latency components of the gastrocnemius muscle were less than 50 microV. Moreover, no correlation was observed between the EMG-A and the MMG(max). The above results suggest that: (1) the muscle tone of the gastrocnemius muscle in rats seems to be regulated by long-latency (supraspinal) reflexes only when the level of EMG activity exceeds a critical threshold of ca 50 microV; (2) when the level of EMG activity is lower, a major role in the resistance of hindlimb muscles is played by some non-neuronal factors; and (3) the proposed animal model emphasizes new aspects of the reflex which may be useful in a search for basic mechanisms underlying changes in the muscle tone.

Animals↗

PubMed1995

The subsensitivity of striatal glutamate receptors induced by chronic haloperidol in rats.

The aim of the present study was to investigate the influence of chronic treatment with haloperidol on the contralateral head turns and rotations induced by intrastriatal agonists of NMDA and non-NMDA receptors in rats. N-Methyl-D-aspartate (NMDA, 500 ng/0.5 mu l), alpha-amino-3-hydroxy-5-methyl-4-isoxasole-propionic acid (AMPA, 1000 ng/0.5 mu l) or kainic acid (50 ng/0.5 mu l), injected into the intermediate and caudal parts of the caudate-putamen, induced contralateral head turns and rotations. Haloperidol was given to animals in a dose of ca. 1 mg/kg per day in drinking water for 6 weeks. On day 5 of withdrawal, haloperidol decreased the number of contralateral head turns, but did not significantly influence the contralateral rotations induced by NMDA, AMPA and kainic acid. At the same time, haloperidol enhanced the stereotypy induced by apomorphine (0.25 mg/kg s.c.). The present results seem to suggest that, apart from supersensitivity to dopamine, chronic treatment with haloperidol also induces subsensitivity of striatal NMDA and non-NMDA receptors.

Animals↗

PubMed1995

Interaction between striatal excitatory amino acid and gamma-aminobutyric acid (GABA) receptors in the turning behaviour of rats.

N-Methyl-D-aspartate (NMDA, 500 ng/0.5 microliters), alpha-amino-3-hydroxy-5-methyl-4-isoxasole-propionic acid (AMPA, 1000 ng/0.5 microliters), or kainic acid (50 ng/0.5 microliters) injected into intermediate and caudal parts of the caudate-putamen induced contralateral head turns and rotations. Picrotoxin (250 ng/0.5 microliters) injected into the same striatal region 30 min before NMDA, AMPA, or kainic acid strongly increased the contralateral turning induced by each of those compounds. The present results suggest that blockade of gamma-aminobutyric acid (GABA)A receptor complex by picrotoxin rendered striatal neurons more sensitive to the action of glutamate on NMDA and non-NMDA receptors.

Animals↗

PubMed1995

Stimulation of glutamate receptors in the intermediate/caudal striatum induces contralateral turning.

The aim of the present study was to investigate the role of striatal NMDA, kainate and AMPA receptors in the turning behaviour of rats. N-methyl-D-aspartate (NMDA, 500 ng/0.5 microliters), kainic acid (50 ng/0.5 microliters) or alpha-amino-3-hydroxy-5-methyl-4-isoxasole- propionic acid (AMPA, 1000 ng/0.5 microliters), injected into the intermediate and caudal parts of the caudate-putamen, induced contralateral head turns and rotations. This effect was delayed or was not observed after administration of the compounds into the globus pallidus. The antagonist of non-NMDA receptors, 6,7-dinitroquinoxaline-2,3-dione (DNQX, 1000 ng/0.5 microliter), antagonized the contralateral head turns and rotations induced by AMPA (1000 ng/0.5 microliter) or kainic acid (50 ng/0.5 microliter), and evoked per se (2000 ng/0.5 microliter) the ipsilateral head turns and rotations. The NMDA receptor antagonist, (+/-)-2-amino-5-phosphonopentanoic acid (AP5, 1000 ng/0.5 microliter), induced mainly ipsilateral head turns and rotations; when injected in a dose of 500 ng/0.5 microliters, it inhibited the contralateral head turns and rotations after NMDA. The results seem to suggest that the contralateral head turns and rotations induced by stimulation of NMDA, AMPA and kainate receptors in the intermediate and caudal parts of the caudate-putamen may result from activation of the gamma-aminobutyrate (GABA)-ergic strionigral pathway.

2-Amino-5-phosphonovalerate↗

PubMed1995

Does reserpine induce parkinsonian rigidity?

The aim of the study was to find out whether the reserpine-induced rigidity is similar to that seen in parkinsonism. Simultaneous measurements of the muscle resistance of the hind foot to passive bending and stretching in the ankle joint, as well as of the electromyographic (EMG) activity of the gastrocnemius and tibialis anterior muscles of rats were carried out. Reserpine was injected in a dose of 10 mg/kg alone or with alpha-methyl-p-tyrosine (250 mg/kg) 1, 4 and 27.5 h before the measurements. Reserpine increased the muscle resistance of the rat's hind leg to passive movements. That effect was the strongest at 1-2 h after the injections, and diminished markedly afterwards. The rigidity was accompanied with an increase in the resting, as well as in the stretch-induced short- and long-latency EMG activity in the gastrocnemius muscle. However, the intensity of the latter symptom did not change for a long period of time, which seems to correlate with the striatal dopamine depletion. The results suggest that the reserpine-increased EMG activity is a good model of parkinsonian rigidity.

Adrenergic Uptake Inhibitors↗

PubMed1994

Involvement of the nucleus accumbens in the myorelaxant effect of baclofen in rats.

The study was designed to search for brain structures responsible for the myorelaxant action of baclofen. Rats were chronically implanted with cannulae in the medial nucleus accumbens (NAS). The muscle tone was increased by reserpine (10 mg/kg i.p.) and measured as a resistance of the hind foot, developed in response to successive passive bendings and straightenings in the ankle joint. (+/-)Baclofen (1 or 2.5 mg/0.5 microliter), injected bilaterally into the NAS 1.5 h after pretreatment with reserpine, decreased the muscle tone of flexors and extensors enhanced by that compound. It is suggested that GABAB receptors of the NAS are involved in the myorelaxant action of baclofen.

Animals↗

PubMed1994

The role of excitatory amino acids in experimental models of Parkinson's disease.

The aim of this article was to review the recent literature on the role of excitatory amino acids in Parkinson's disease and in animal equivalents of parkinsonian symptoms. Effects of NMDA and AMPA antagonists on the reserpine-induced akinesia, catalepsy and rigidity, on the neuroleptic-induced catalepsy, on the turning behaviour of 6-OHDA-lesioned rats, as well as on the parkinsonian symptoms evoked by MPTP in monkeys were analysed. Moreover, the role of NMDA antagonists in Parkinson's disease was discussed. Data concerning the protective influence of these drugs on degenerative properties of methamphetamine, MPTP and 6-OHDOPA were also presented. On the basis of the above findings, the following conclusions may be drawn: (1) disturbances in the glutamatergic transmission in various brain structures seem to play a significant role in the development of symptoms of Parkinson's disease; (2) the NMDA-receptor blocking component may make a substantial contribution to the therapeutic effect of antiparkinsonian drugs; a similar contribution of AMPA-receptor blocking component has not been sufficiently documented, so far; (3) compounds blocking NMDA receptors may possibly prevent the development of Parkinson's disease; this presumption needs, however further studies; (4) side effects of NMDA receptor antagonists may be a limiting factor in the use of these compounds in humans.

Amphetamine↗

PubMed1994

Antiparkinsonian action of MK-801 on the reserpine-induced rigidity: a mechanomyographic analysis.

MK-801, a non-competitive antagonist of NMDA receptors, is known to exhibit a beneficial action in many animal models of Parkinson's disease. The aim of this study was to examine the influence of MK-801 on the reserpine-induced muscle rigidity. The rigidity was estimated by a direct mechanomyographic method. This method consists in successive bending and straightening of a rat's hind foot in the ankle joint and measuring the resistance of the foot to passive movements. Reserpine in doses of 5-10 mg/kg ip, given alone or in combination with alpha-methyl-p-tyrosine (alpha MT, 250 mg/kg ip), induced rigidity. The strongest muscle rigidity was induced by 10 mg/kg of reserpine 1 hour after administration. MK-801 (0.32-1.28 mg/kg sc) injected 70 min after reserpine (10 mg/kg ip) decreased the rigidity induced by the latter compound. Similarly, MK-801 (1.28 mg/kg sc), administered 27 h 40' after joint treatment with reserpine (10 mg/kg ip) and alpha MT (250 mg/kg ip), strongly inhibited the reserpine-induced muscle rigidity. The obtained results show that the glutamatergic hyperactivity plays a significant role in the reserpine-induced rigidity. As the reserpine-induced motor disturbances are commonly accepted to be an animal model of parkinsonian symptoms, it may be assumed that the NMDA receptor blocking component may contribute substantially to the therapeutic action of antiparkinsonian drugs.

Animals↗

PubMed1994

Genotypic differences in locomotor stimulation and dopaminergic activity following acute ethanol administration.

The effects of increasing doses of ethanol on locomotor activity and on the metabolism of dopamine (DA) in the limbic forebrain and in the striatum of CBA, C57, and NMRI mice were studied. In NMRI mice, low doses of ethanol produced locomotor stimulation which was followed by inhibition of locomotor activity at higher doses. In C57 and CBA animals, ethanol caused only reduction of locomotor activity. A low dose of ethanol (2.25 g/kg, i.p.) produced a significant enhancement of the release of dopamine (measured as the ratio DOPAC/DA) in limbic brain structures of all animals with no corresponding effect in the striatum. A high dose of ethanol (4.5 g/kg, i.p.) significantly increased the DOPAC/DA ratio both in the limbic forebrain and in the striatum of all animals. The significance of these behavioral and biochemical observations with regard to genetic aspects of the role of DA in the stimulatory/reinforcing properties of ethanol and to previously observed genetic differences in other neurotransmitter systems, especially GABA and glutamate, is discussed.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1993

Zona incerta-lateral hypothalamus as an output structure for impulses involved in neuroleptic drug-induced catalepsy.

Our previous studies showed that the neuronal impulses connected with catalepsy, which have their origin at dopamine D2 receptors in the ventro-rostral part of the nucleus caudatus-putamen in rats, are conveyed to the zona incerta-lateral hypothalamic region. The aim of the present study was to investigate the route of the neuronal impulses between these structures. The experiments were carried out on rats with cannulae chronically implanted in the brain structures. We showed that (1) bilateral injection of bicuculline methiodide (5-50 ng) into the ventro-medial part of the globus pallidus (GPv) and (2) bilateral injection of muscimol (2.5-25 ng) into the substantia nigra pars reticulata (SNR) inhibit, in a dose dependent manner, the catalepsy induced by sulpiride (1 microgram) administered bilaterally into the ventro-rostral part of the nucleus caudatus-putamen. It was also demonstrated that muscimol (25 ng), injected bilaterally into the ventro-medial part of the globus pallidus, induces catalepsy which, in turn, is dose-dependently inhibited by either (1) muscimol (5-25 ng) injected into the substantia nigra pars reticulata, or (2) bicuculline (1.0-2.5 ng) injected into the zona incerta-lateral hypothalamus (ZI-LH). Moreover, even a dose as high as 50 ng of bicuculline, injected into the ventro-medial part of the globus pallidus, had no significant effect on the locomotor activity of rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Direct mechanomyographic measurement of the myorelaxant action of baclofen and diazepam in normal and reserpinized rats.

A pathologically increased muscle tone is frequently observed. Objective methods for measuring directly the muscle-relaxant action of drugs in laboratory animals are scarce. This study shows that a computerized mechanomyographic method allows the assessment of myorelaxant drugs. The method consists of the successive bending and straightening of the rat's foot in the ankle joint and the separate measurement of resistance of extensors and flexors of the hind foot to passive movements. The two well-known antispastic drugs diazepam and baclofen reduced the normal muscle tone in both groups of muscles in non-treated animals as well as the muscle tone increased by reserpine (10 mg/kg i.p.). The results obtained show that the mechanomyographic method directly and reliably reveals the myorelaxant action of drugs.

Analysis of Variance↗

PubMed1992

Muscle stiffness and continuous electromyographic activity in old rats; an animal model for spasticity?

A mechanomyographic response of the hind foot to passive straightening and bending, as well as an electromyographic activity of the gastrocnemius and tibialis anterior muscles were recorded in old (35-44-month-old) and young female rats. In old rats, spontaneous, tonic electromyographic activity patterns were concurrently observed in both antagonistic muscles; they were low-amplitude, dense tonic activity and continuous, high-amplitude, sparse electromyographic activity. The tonic electromyographic activity was correlated with a decline in the strength and mass of muscles, as well as with motor disturbances, including paresis of the rigidly straightened backward hind legs, dragged behind by an animal. In muscles of old rats, morphological features of a chronic denervation atrophy were found. Baclofen (10 and 15 mg/kg, i.p.) diminished the spontaneous tonic electromyographic activity and potently decreased the whole body muscle tone, whereas Madopar (50 mg/kg of L-DOPA+12.5 mg/kg of benerazide) was ineffective. It is suggested that old rats in which the above-described pathologic alterations are observed might be a useful animal model in the search for basic etiopathological mechanisms of spasticity and similar disturbances found in humans.

Aging↗

PubMed1991

Effect of the NMDA receptor antagonist, MK-801, on locomotor activity and on the metabolism of dopamine in various brain areas of mice.

Various doses (0.1-0.5 mg/kg i.p.) of the N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, produced a dose-dependent increase in well-coordinated locomotor activity of NMRI mice. Higher doses (greater than 0.5 mg/kg) produced a typical motor syndrome characterized by head weaving, body rolling, ataxia and salivation. MK-801, 0.2 mg/kg i.p., a dose which produced marked locomotor stimulation, increased the rate of disappearance of dopamine in the striatum and in the limbic forebrain of the animals, whereas the rate of disappearance of noradrenaline remained unchanged in the limbic forebrain and in the hippocampus. MK-801 increased the rate of tyrosine hydroxylation (measured as the accumulation of 3,4-dihydroxyphenylalanine (DOPA) after inhibition of DOPA decarboxylase) in the striatum with no change in DOPA formation in the limbic forebrain. The levels of 3,4-dihydroxyphenylacetic acid (DOPAC) remained unchanged both in the striatum and in the limbic forebrain following the administration of MK-801. It is concluded that MK-801 may facilitate the activation of dopaminergic mechanisms through an indirect (perhaps by reducing glutamatergic activity) rather than a direct effect on dopamine neurons.

Animals↗