Biomedical subjects

K Ossowska

Publications and source records attributed to K Ossowska.

At least 55 records · Page 3Linked to original sources

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↗

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↗

PubMed1988

Evidence for the independent role of GABA synapses of the zona incerta-lateral hypothalamic region in haloperidol-induced catalepsy.

Bicuculline (0.5-50 ng), injected bilaterally into the zona incerta-lateral hypothalamus (ZI-LH) of the rat, inhibited catalepsy evoked by haloperidol (1 mg/kg s.c.) in a dose-dependent manner. The same effect was obtained by injections of bicuculline directed towards the ventromedial thalamic nucleus (Vm), but then higher doses of the drug were necessary (10-50 ng). Muscimol (10-50 ng), injected into the ZI-LH, evoked a state of catalepsy almost identical to that of haloperidol. Bicuculline (50 ng) abolished the catalepsy evoked by muscimol (25 ng). Bicuculline injected into ZI-LH in doses of 0.5-2.5 ng did not change locomotor activity of rats as measured in photoresistor actometers, whereas it had a slightly stimulating effect at a dose of 5 ng. A comparison between the doses of bicuculline injected into the ZI-LH and Vm suggests that, irrespective of Vm synapses, GABA synapses of this region are involved in the mediation of haloperidol-induced catalepsy. A similar conclusion regarding the catalepsy and rigidity induced by morphine was drawn previously. It seems, therefore, that the catalepsy antagonism of bicuculline is independent of the action of the drug which promotes the locomotor stimulation.

Animals↗

PubMed1988

The role of the ventromedial thalamic nucleus in the catalepsy evoked from the substantia nigra pars reticulata in rats.

Picrotoxin (25, 50 and 100 ng), injected unilaterally into the posterior part of the substantia nigra pars reticulata (SNR) of rats, evoked a dose-dependent catalepsy. The catalepsy evoked by 100 ng of picrotoxin injected into the SNR was abolished by a subsequent bilateral injection of the same drug (200 ng) into the ventromedial thalamic nuclei. It is suggested that impulses pertinent to the catalepsy evoked from the SNR are transmitted via a GABAergic pathway to the ventromedial thalamic nucleus, wherefrom they reach the striatum, as had been shown previously.

Animals↗

PubMed1987

The role of gamma-aminobutyric acid mechanisms of the zona incerta-lateral hypothalamus in the catalepsy and muscle rigidity evoked by morphine.

Picrotoxin or bicuculline were injected bilaterally into the zona incerta-lateral hypothalamus (ZI-LH) of the rat. Each drug (50 ng) inhibited or abolished the catalepsy induced by 20 mg/kg s.c. of morphine. Each drug also strongly inhibited the tonic electromyographic activity (EMG) induced by 10 mg/kg s.c. of morphine in the gastrocnemius soleus muscle (GS). The obtained results demonstrate participation of the ZI-LH in both catalepsy and rigidity induced by a systemic administration of morphine.

Animals↗

PubMed1987

The neostriatal inhibition of catalepsy, but not of muscle rigidity, evoked from the substantia nigra pars reticulata.

The effects of a bilateral blockade of neo- and palleostriatal GABAergic mechanisms on catalepsy and muscle rigidity resulting from picrotoxin injection into the substantia nigra pars reticulata (SNR) were studied. The catalepsy and rigidity were induced by a unilateral injection of 100 ng/0.5 microliter of picrotoxin. Bilateral injections of 250 ng/l microliter of picrotoxin into the intermediate-ventral parts of the caudato-putamen (CP) abolished the catalepsy but had no effect on the muscle rigidity induced by an intranigral injection of the drug. Bilateral injections of 250 ng/l microliter of picrotoxin into the globus pallidus (GP) did not influence the catalepsy and rigidity induced by the intranigral injection of the drug. The results indicate that the impulses, connected with the catalepsy evoked from the SNR seem to be transmitted back to the CP and blocked therein by inhibition of GABAergic synapses in its intermediate-ventral part. The impulses, connected with the muscle rigidity evoked from the SNR, presumably do not return to the striatum.

Animals↗

PubMed1986

GABA mechanisms of ventromedial thalamic nucleus in morphine-induced muscle rigidity.

The aim of the study was to investigate the role of the ventromedial thalamic nucleus in the rigidity induced by morphine. Muscle rigidity was assessed using an electromyographic method (EMG) in non-anaesthesized rats with electrodes implanted unilaterally in the gastrocnemius soleus muscle. Subcutaneous (s.c.) injections of morphine in doses of 5, 10 or 20 mg/kg evoked tonic EMG activity in the gastrocnemius soleus muscle; this was estimated as muscle rigidity. Picrotoxin was injected bilaterally into the ventromedial nucleus in doses of 50-400 ng/0.5 microliter 30 min after morphine administration. Picrotoxin in doses of 200 and 400 ng attenuated the tonic EMG activity induced by morphine, 10 mg/kg s.c. Picrotoxin in a dose of 400 ng reduced the tonic activity induced by morphine, 20 mg/kg s.c. The results suggest that the thalamic ventromedial nucleus mediates the morphine-induced rigidity.

Animals↗

PubMed1985

Thalamus as a relay station for catalepsy and rigidity.

The aim of the study was to determine to what extent catalepsy and tonic rigidity of muscles induced by muscimol administration into the ventral thalamic nuclei disturb the motor activity of rats. This study also aimed to test whether the ventromedial thalamic nucleus (Vm) was involved in transmitting effects evoked by the systemic injection of neuroleptics or opioids. For this purpose muscimol and/or picrotoxin was injected into the ventral thalamic nuclei and the behaviour of the animals was assessed in a series of test situations. It was found that muscimol administration to the Vm disturbs not only the initiation and performance of voluntary movements but also the occurrence of avoidance when the animal's life is endangered. Postural reflexes remained, however, undisturbed. Those effects seemed to be GABA- and site-specific to Vm. The haloperidol catalepsy was strongly inhibited by administration of picrotoxin to the Vm while the morphine catalepsy remained unchanged after picrotoxin. The Vm plays a crucial role in the motor behaviour and transmission of cataleptogenic effects of haloperidol, whereas similar effects produced by morphine appear to by-pass the investigated thalamic region.

Animals↗

PubMed1984

The role of the GABA mechanisms of the globus pallidus in mediating catalepsy, stereotypy and locomotor activity.

Muscimol, picrotoxin and bicuculline were injected bilaterally through permanently implanted cannulae into either anterior (GPa) or posterior parts of the globus pallidus (GPp) of rats. Both the muscimol injected into the GPa and the picrotoxin injected into the GPp abolished or strongly inhibited spiperone (0.2 mg/kg, IP)-induced catalepsy. Muscimol alone (25-200 ng/0.2 microliter/GP) injected into the GPa evoked a dose-dependent biphasic effect: at first catalepsy (throughout 7.3 min), and then a long-lasting (more than 2 hr) locomotor stimulation and stereotyped sniffing. Muscimol (200 ng/GP) injected into GPp inhibited both the spontaneous motility and amphetamine-induced hyperactivity. Picrotoxin (200 and 400 ng/GP) injections into GPa and GPp produced an increase of the locomotor activity as well as stereotyped sniffing. Picrotoxin started to block muscimol hyperactivity when its own stimulatory action disappeared, thus also for picrotoxin the second phase of action could be detected. The globus pallidus is shown to be a relay station of impulses mediating neuroleptic catalepsy. Furthermore, it is suggested that behavioural changes induced by muscimol resulted from the action of the drug on at least 2 different neuronal systems, both being controlled by GABA receptors. One of them seems to be responsible for inducing neuroleptic-like catalepsy, and the other one for the hyperactivity and blockade of spiperone-catalepsy.

Animals↗

PubMed1983

A biphasic influence of globus pallidus lesions: spontaneous catalepsy followed by anticataleptic effect.

The behavioural and histological effects of unilateral or bilateral lesions induced by kainic acid injections into the globus pallidus were investigated in rats. Both lesions provoked a behavioural syndrome similar to those seen in animals treated systemically with neuroleptics or opiates. Animals displayed akinesia, ptosis, catalepsy, hypothermia and muscular rigidity. Also a marked hypersensitivity to touch, and a sensory neglect to touch and pain limited to hindlegs, adipsia, aphagia and high mortality of lesioned rats were observed. These symptoms were much stronger and lasted longer (catalepsy lasted over 15 days) in bilaterally lesioned animals. Subcutaneous injections of apomorphine in bilaterally lesioned rats abolished akinesia and catalepsy while rigidity and ptosis were unaffected. In unilaterally lesioned rats in which the lesion-induced spontaneous catalepsy already disappeared the spiperone-induced catalepsy was suppressed while in bilaterally lesioned animals which showed still pronounced lesion-induced catalepsy the spiperone-induced catalepsy was unchanged when compared to the sham-operated rats. Our results and the literature data suggest that the lesions of the globus pallidus produce biphasic effects: spontaneous catalepsy and unchanged neuroleptic catalepsy in the first phase and suppression of the neuroleptic catalepsy in the second phase. The role of the globus pallidus as a distal link (for neostriatum and n. accumbens) in neuronal chain forming a matrix of central patterns of catalepsy, akinesia and rigidity is discussed.

Animals↗

PubMed1979