Biomedical subjects

S Wolfarth

Publications and source records attributed to S Wolfarth.

At least 19 recordsLinked to original sources

PubMed1998

Contribution of the glycine site of NMDA receptors in rostral and intermediate-caudal parts of the striatum to the regulation of muscle tone in rats.

The aim of the present study was to assess the contribution of the glycine site of NMDA receptors in the striatum to the regulation of muscle tone. Muscle tone was examined using a combined mechanoand electromyographic method, which measured simultaneously the muscle resistance (MMG) of the rat's hind foot to passive extension and flexion in the ankle joint and the electromyographic activity (EMG) of the antagonistic muscles of that joint: gastrocnemius and tibialis anterior. Muscle rigidity was induced by haloperidol (2.5 mg/kg i.p.). 5,7-dichlorokynurenic acid (5,7-DCKA), a selective glycine site antagonist, injected in doses of 2.5 and 4.5 microg/0.5 microl bilaterally, into the rostral region of the striatum, decreased both the haloperidol-induced muscle rigidity (MMG) and the enhanced electromyographic activity (EMG). 5,7-DCKA injected bilaterally in a dose of 4.5 microg/0.5 microl into the intermediate-caudal region of the striatum of rats not pretreated with haloperidol had no effect on the muscle tone. The present results suggest that blockade of the glycine site of NMDA receptors in the rostral part of the striatum may be mainly responsible for the antiparkinsonian action of this drug.

Animals↗

PubMed1998

LY354740, a group II metabotropic glutamate receptor agonist with potential antiparkinsonian properties in rats.

The aim of this study was to examine whether (+)-2-aminobicyclo[3.1.0]-hexane-2,6-dicarboxylate monohydrate (LY354740), a selective agonist of group II metabotropic glutamate receptors, possesses antiparkinsonian properties. Parkinsonian-like muscle rigidity was induced by pretreatment with haloperidol (1 mg/kg i.p.). It was measured as increased resistance developed by the rat's hind leg to passive extension and flexion. LY354740 (5 and 10 mg/kg i.p.) dose-dependently diminished the haloperidol-induced muscle rigidity. The present results suggest that LY354740 counteracts the muscle rigidity in an animal model of parkinsonism.

Animals↗

PubMed1998

Muscle rigidity induced by fluphenazine in rats is antagonized by L-DOPA, an antiparkinsonian drug.

The aim of the present study was to find out whether the classic neuroleptic fluphenazine is a good model compound for inducing parkinsonian-like muscle rigidity in rats. The muscle tone was measured as resistance developed by the rat's hind foot to passive flexion and extension. Fluphenazine in doses of 0.4-3.0 mg/kg i.p. induced a dose-dependent increase in the hind foot resistance to passive movements. The muscle rigidity induced by fluphenazine 1.5 mg/kg i.p.) was counteracted in a dose-dependent manner by the main antiparkinsonian drug L-DOPA (25-75 mg/kg i.p.). The present results suggest that the fluphenazine-induced muscle rigidity may be a useful model of parkinsonian rigidity.

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

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

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↗

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↗

PubMed1990

Striatal and nucleus accumbens D1/D2 dopamine receptors in neuroleptic catalepsy.

Haloperidol (2.5-10 micrograms) injected bilaterally into the ventro-rostral striatum or into the nucleus accumbens induced dose-dependent catalepsy whereas its injection into the dorso-rostral striatum (2.5 micrograms) was ineffective. Similarly, the specific antagonist of D1 receptors, SCH 23390 (1-5 micrograms), injected into the ventro-rostral striatum or nucleus accumbens, as well as the specific antagonist of D2 receptors, sulpiride, injected into the ventro-rostral striatum (0.02-15 micrograms) or nucleus accumbens (1-15 micrograms), induced a dose-dependent catalepsy. Both drugs (SCH 23390 2 micrograms, sulpiride 0.5 micrograms) were ineffective when injected into the dorso-rostral striatum. Doses of sulpiride about 100 times lower than those injected into the nucleus accumbens were sufficient to evoke an equipotent catalepsy when injected into the ventro-rostral striatum. However, similar doses of haloperidol and SCH 23390, injected into the ventro-rostral striatum and nucleus accumbens, evoked a similar catalepsy. It is concluded that (1) the catalepsy induced by systemic administration of haloperidol seems to result from the action of this drug on both the ventro-rostral striatum and the nucleus accumbens, (2) both D1 and D2 dopamine receptors in the ventro-rostral striatum are involved in the cataleptogenic action of neuroleptics, and (3) in the nucleus accumbens, only D1 dopamine receptors seem to play an important role in this phenomenon.

Animals↗

PubMed1990

Lateral hypothalamus-zona incerta region as an output station for the catalepsy induced by the blockade of striatal D1 and D2 dopamine receptors.

Our previous study reported that the blockade of GABAA receptors of the lateral hypothalamus-zona incerta region (LH-ZI) by local injections of bicuculline methiodide inhibited the haloperidol-induced catalepsy. The aim of the present study was to determine (1) whether the blockade of GABAA receptors of the LH-ZI may counteract the catalepsy evoked by SCH 23390 and by sulpiride, and (2) whether the GABAA receptors of the LH-ZI affect the function of the striatal dopaminergic system. Bicuculline methiodide (2.5 and 5 ng/side) injected bilaterally into the LH-ZI inhibited in a dose-dependent manner the catalepsy induced by SCH 23390 administered peripherally (0.2 mg/kg s.c.). SCH 23390 (2 micrograms/side) and sulpiride (1 microgram/side) injected bilaterally into the rostroventral part of the striatum induced potent catalepsy. The catalepsy induced by injection of SCH 23390 (2 micrograms) and sulpiride (1 microgram) into the striatum was inhibited by bicuculline methiodide (2.5 ng and 5 ng) injected into the LH-ZI. Neither bicuculline (5 ng/side) nor muscimol (50 ng/side) injected bilaterally into the LH-ZI changed the levels of dopamine and its intraneuronal metabolite, 3,4-dihydroxyphenyl-acetic acid, or the concentration of noradrenaline and 5-hydroxyindole-acetic acid measured in the striatum and nucleus accumbens by HPLC with an electrochemical detection. It is concluded that GABAA receptors of the LH-ZI are an output station for the catalepsy induced by the blockade of the striatal D2 and D1 dopamine receptors.

Animals↗

PubMed1989

Can the supersensitivity of rodents to dopamine be regarded as a model of tardive dyskinesia?

1. The paper presents arguments derived from both, clinical work and animal experiments, for or against the traditional hypothesis suggesting that tardive dyskinesia (TD) is caused by supersensitivity to dopamine. The main aim of this study was to answer the question posed in the title - whether the supersensitivity to dopamine evoked in rodents by neuroleptics can be regarded as an adequate pharmacological model of TD. 2. The data presented here prove that chronic administration of neuroleptics to schizophrenic patients cannot be the only factor inducing TD; furthermore, symptoms similar or identical to those of TD are also observed in the course of other disorders, not connected with neuroleptics, e.g. aging or schizophrenia itself. 3. Clinical data offer no clear evidence for the existence of a direct cause-effect relationship between super-sensitivity to dopamine and occurrence of TD. 4. The role of brain degeneration, caused by different factors but in particular by the process of aging, in the pathogenesis of dyskinetic disorders, including TD, has been stressed. 5. Pharmacological and biochemical data show that chronic administration of classic neuroleptics to animals induces an increase in the density of dopamine D-2 receptors (Bmax). It seems that this receptor-mediated supersensitivity may concern both the postsynaptic and the presynaptic D-2 dopamine receptors. On the other hand, it is not clear enough whether a dopamine D-1 receptor-mediated supersensitivity might also be a causal factor of TD. 6. The analysis in animals, of biochemical and pharmacological effects of neuroleptics which do not induce TD showed that in some situations these drugs may also evoke the receptor-mediated supersensitivity concerning dopamine D-2 receptors. 7. The method of a prolonged (approx. 1 year) oral administration of neuroleptics seems to differentiate those which induce TD from those which do not, at least regarding the induction of an increase of Bmax for butyrophenone neuroleptics and an increase of apomorphine-induced stereotypy, however, some exceptions are noted. 8. The above analysis of clinical and experimental data suggests that the supersensitivity to dopamine in rats treated chronically with neuroleptics cannot be accepted as a model which reflects the etiopathogenesis of TD. Neither a positive nor a negative result obtained in this test is reliable enough, and either depends on the tested parameters (apomorphine stereotypy and [3H]spiperon binding seem to be the most reliable), route of neuroleptic administration, duration of treatment and, probably, a number of other, still unknown factors.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗