Biomedical subjects

J Wardas

Publications and source records attributed to J Wardas.

13 recordsLinked to original sources

PubMed1996

Blockade of A2a adenosine receptors positively modulates turning behaviour and c-Fos expression induced by D1 agonists in dopamine-denervated rats.

In rats with unilateral 6-hydroxydopamine lesions of the dopaminergic nigrostriatal pathway, administration of the A2a adenosine antagonist SCH 58261 alone did not induce any motor asymmetry but strongly potentiated the contralateral turning behaviour induced by the dopamine D1 agonist SKF 38393. SCH 58261 also increased the number of Fos-like positive nuclei induced by SKF 38393 in the 6-hydroxydopamine-lesioned striatum. Intense potentiation of D1-dependent turning behaviour and c-Fos expression was also observed after administration of the A2a/A1 antagonist CGS 15943. Administration of the A1 adenosine receptor antagonist DPCPX induced a small potentiation of D1-mediated contralateral turning while c-Fos expression induced by SKF 38393 was not modified. The results suggest that endogenous adenosine acting on A2a receptors can exert an inhibitory influence on the functional expression of D1-mediated responses in dopamine-denervated rats, and propose new possible therapeutic approaches in the treatment of Parkinson's disease.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

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↗

PubMed1995

Adenosine A2 receptors stimulate c-fos expression in striatal neurons of 6-hydroxydopamine-lesioned rats.

The induction of the early-gene c-fos after administration of the adenosine A2a receptor agonist CGS 21680, was studied in the striatum of normal rats or in rats with a unilateral 6-hydroxydopamine lesion of the dopaminergic nigrostriatal neurons. CGS 21680 (2.25 mg/kg) induces c-fos expression in the 6-hydroxydopamine-lesioned striatum, while up to 40 mg/kg fails to induce c-fos in the intact striatum or in the striatum of normal rats. Blockade of muscarine receptors by scopolamine (5 mg/kg) partially prevents, and stimulation of dopamine D2 receptors by quinpirole (0.5 mg/kg) completely reverses, CGS 21680-induced c-fos expression in the 6-hydroxydopamine-lesioned striatum. In turn, CGS 21680 partially reverses c-fos expression induced by quinpirole in the lesioned globus pallidus. CGS 21680, in addition, dose-dependently reduces the turning behavior induced by quinpirole (0.5 mg/kg) in 6-hydroxydopamine-lesioned rats. The results suggest that CGS 21680 induces c-fos expression in the striatum through direct and indirect mechanisms related to the ability of A2a receptors to stimulate cyclic AMP formation or acetylcholine release which in turn would activate c-fos through muscarinic receptors.

Adenosine↗

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↗

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↗

PubMed1990

Evidence for a role of glycine in area tempestas for triggering convulsive seizures.

An epileptogenic region of the deep prepiriform cortex, area tempestas (AT), triggers convulsive seizures in response to the focal application of GABA antagonists, muscarinic agonists and excitatory amino acid agonists. In all cases, activation of N-methyl-D-aspartate (NMDA)-sensitive receptors in AT is required for triggering convulsions from this site. To determine whether glycine is involved in the activation of NMDA-sensitive receptors in AT, we evaluated the effects of 7-chlorokynurenic acid (7-CLKYN); kynurenic acid (KYN) and 3-amino-1-hydroxy-2-pyrrolidone (HA-966) on convulsions evoked by focal application of bicuculline methiodide (118 pmol) into AT. Significant anticonvulsant effects were obtained with 1.25 nmol of 7-CLKYN, 6.25 nmol of KYN and 60 nmol of HA-966 in AT. 7-CLKYN in AT also blocked the convulsant effects of carbachol (273 pmol) and kainic acid (117 pmol) injected into AT. When injected into the lateral ventricle, high doses (50-100 nmol) of 7-CLKYN were required in order to attenuate AT-evoked convulsions and these doses produced marked ataxia. In contrast, no ataxia was observed following 7-CLKYN application into AT at anticonvulsant doses. Our results implicate glycine antagonism as a mechanism for preventing convulsions triggered via NMDA receptor activation in AT and demonstrate that a different anatomical site of action is responsible for the motor impairment produced by glycine antagonism.

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↗

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↗

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↗

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↗

PubMedDate not supplied

Further evidence for the subsensitivity of striatal AMPA receptors, induced by chronic haloperidol administration: an autoradiographic study.

The aim of the present study was to investigate the influence of chronic treatment with haloperidol on the striatal N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxasole-propionic acid (AMPA) and dopamine D2 receptors using a quantitative autoradiography in rats. Haloperidol was given to animals in a dose of ca. 1 mg/kg/day in drinking water for 6 weeks or 3 months and was afterwards withdrawn for 5 days. Haloperidol increased by 20-50% the binding of [3H]spiperone in different regions of the caudate-putamen. Haloperidol decreased by ca. 30% the binding of [3H]AMPA in the ventrolateral region of intermediate part of the caudate-putamen, but did not influence the binding of [3H]MK-801. The present results suggest that, apart from supersensitivity to dopamine, chronic treatment with haloperidol also induces subsensitivity of striatal AMPA receptors.

Animals↗

PubMedDate not supplied

Specific involvement of striatal D1 and D2 dopamine receptors in the neuroleptic catalepsy in rats.

Since highly specific antagonists of D1 (SCH 39166) and D2 (raclopride) dopamine receptors have recently become available, we decided to investigate the role of striatal populations of these receptors in catalepsy - an animal model of neuroleptic-induced parkinsonism in humans. Injections of raclopride (2.5, 5 and 10 micrograms/0.5 microliters) into the ventro-rostral part of the striatum induced a strong, dose-dependent and long-lasting catalepsy. Intrastriatal injections of SCH 39166 (1.5 and 3.6 micrograms/ 0.5 microliters) also evoked a dose-dependent, but short-lasting catalepsy. The present results suggest, that neuroleptic side-effects are specifically dependent on the blockade of D2 and D1 dopamine receptors in the striatum.

Animals↗