The aim of the present study was to examine the influence of the long-term paraquat administration on the dopaminergic nigrostriatal system in rats. Paraquat was injected at a dose of 10 mg ⁄ kg i.p. for 4–24 weeks. We found that this... more
The aim of the present study was to examine the influence of the long-term paraquat administration on the dopaminergic nigrostriatal system in rats. Paraquat was injected at a dose of 10 mg ⁄ kg i.p. for 4–24 weeks. We found that this pesticide reduced the number of tyrosine hydroxylase-immunoreactive neurons of the substantia nigra; after the 4-week treatment the reduction (17%, nonsignificant) was confined to the rostrocentral region of this structure but, after 24 weeks, had spread along its whole length and was % 37%. Moreover, it induced a biphasic effect on dopaminergic transmission. First, levels of dopamine, its metabolites and turnover were elevated (4–8 weeks) in the caudate–putamen, then all these parameters returned to control values (12 weeks) and dropped by 25–30% after 24 weeks. The binding of [ 3 H]GBR 12,935 to dopamine transporter in the caudate–putamen was decreased after 4–8 weeks, then returned to control values after 12 weeks but was again decreased after 24 weeks. Twenty-four-week paraquat administration also decreased the level of tyrosine hydroxylase (Western blot) in the caudate–putamen. In addition, paraquat activated serotonin and noradrenaline transmission during the first 12 weeks of treatment but no decreases in levels of these neurotransmitters were observed after 24 weeks. The above results seem to suggest that long-term paraquat administration produces a slowly progressing degeneration of nigrostriatal neurons, leading to delayed deficits in dopaminergic transmission, which may resemble early, presymptomatic, stages of Parkinson's disease.
Research Interests:
Selective toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a parkinsonism inducing compound, is well known to be related to an uptake of its active metabolite MPP + into dopaminergic neurons by dopamine transporter (DAT).... more
Selective toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a parkinsonism inducing compound, is well known to be related to an uptake of its active metabolite MPP + into dopaminergic neurons by dopamine transporter (DAT). The aim of the present study was to examine whether paraquat, a commonly used herbicide, which is an 1-methyl-4-phenyl-pyridinium ion (MPP +) analogue, affects DAT in vivo in rats. Paraquat administered at a dose of 10 mg/kg ip decreased the binding of [ 3 H]GBR 12,935 to DAT measured by quantitative autoradiography in the dorsal and ventral caudate-putamen, but not in the substantia nigra pars compacta. Moreover, this compound increased the level of 3-methoxytyramine (3-MT) and 3-MT/dopamine ratio in the anterior and posterior caudate-putamen measured by HPLC with electrochemical detection. No other alterations in the levels of dopamine and its metabolites were found in the caudate-putamen and substantia nigra. The present study seems to suggest that systemic paraquat administration affects striatal DAT and dopamine metabolism in the nigrostriatal neurons in rats which may be crucial for its neurotoxic effects on dopaminergic neurons.
Research Interests:
—A deficiency of the dopaminergic transmission in the mesocortical system has been suggested to contribute to cognitive disturbances in Parkinson's disease. Therefore, the aim of the present study was to examine whether the long-term... more
—A deficiency of the dopaminergic transmission in the mesocortical system has been suggested to contribute to cognitive disturbances in Parkinson's disease. Therefore, the aim of the present study was to examine whether the long-term administration of a commonly used herbicide, para-quat, which has already been found to induce a slowly progressing degeneration of the nigrostriatal neurons, influences mesocortical dopaminergic neurons in rats. Para-quat at a dose of 10 mg/kg i.p. was injected either acutely or once a week for 4, 8, 12 and 24 weeks. Acute treatment with this pesticide increased the level of homovanillic acid (HVA) and HVA/dopamine ratio in the prefrontal cortex. After 8 weeks of administration paraquat increased the number of stereologically counted tyrosine hydroxylase– immunoreactive (TH-ir) neurons and their staining intensity in the ventral tegmental area (VTA), which is a source of the mesocortical dopaminergic projection. At the same time, few TH-ir neurons appeared in different regions of the cerebral cortex: in the frontal, cingulate, retrosplenial and parietal cortices. Chronic paraquat administration did not influence the level of dopamine in the prefrontal cortex but increased the levels of its metabolites: 3,4-dihydroxyphe-nylacetic acid (after 8 –12 weeks), HVA (after 4 and 12 weeks) and HVA/dopamine ratio (4 weeks). After 24 weeks this pesticide reduced the number of TH-ir neurons in the VTA by 42% and of the Nissl-stained neurons by 26%, and induced shrinkage of this structure by ca. 25%. Moreover, TH-ir neurons in the cortex were no more visible after such a long period of administration and levels of dopamine metabolites returned to control values. The present results suggest that the long-term paraquat administration destroys dopaminergic neurons of the VTA. However, compensatory activation of the VTA neurons and cortex overcomes progressing degeneration and maintains cortical dopaminergic transmission.
Research Interests:
Depression is a frequent comorbid disorder in Parkinson's disease (PD) which may precede appearance of its motor symptoms by several years. Pathomechanisms underlying PD have been suggested to be responsible for the PD-related depression.... more
Depression is a frequent comorbid disorder in Parkinson's disease (PD) which may precede appearance of its motor symptoms by several years. Pathomechanisms underlying PD have been suggested to be responsible for the PD-related depression. The aim of the study was to examine the influence of a partial lesion of striatal dopaminergic terminals on the " depressive-like " behavior of rats in the forced swimming test (FS). 6-Hydroxydopamine (6-OHDA) was injected bilaterally into the ventro-lateral region of the caudate-putamen (CP) (3.75 µg/2.5 µl/side). The locomotor activity and behavior of rats in the FS were measured 2 and 4 weeks after the operation. The lesion extent was analyzed by biochemical and immunohistochemical methods. Two weeks after the operation, the 6-OHDA-treated rats displayed a prolonged immobility in the FS. This effect disappeared after 4 weeks. The locomotor activity was not influenced by 6-OHDA. Levels of dopamine, DOPAC and HVA were decreased in the nucleus accumbens (NAC) 2 weeks after 6-OHDA but were not changed in the CP, frontal cortex (FCX) and substantia nigra (SN). No significant effect of 6-OHDA on tyrosine hydroxylase-immunoreactivity in the CP and NAC were found. The present study indicates that a relatively small lesion of dopaminergic terminals in the ventral striatum, which does not produce any motor disturbances, may induce " depressive-like " symptoms.
Research Interests:
Paraquat is a toxin suggested to contribute to pathogenesis of Parkinson’s disease. The aim of the present study was to examine toxic influence of subchronic treatment with this pesticide (5 days, one injection per day, 2–3 days of... more
Paraquat is a toxin suggested to contribute to pathogenesis of Parkinson’s disease. The aim of the present study was to examine toxic influence of subchronic treatment with this pesticide (5 days, one injection per day, 2–3 days of withdrawal) on dopaminergic, serotonergic, noradrenergic and GABAergic neurons. Paraquat decreased the number of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the substantia nigra by 22% (measured 3 days after withdrawal). Two days after withdrawal the levels of the dopamine metabolites and dopamine turnover in the caudate–putamen, substantia nigra and prefrontal cortex were reduced by ca. 20–60%, and the binding of [3H]GBR 12,935 to dopamine transporter dropped by 25–40% in the caudate–putamen. Three days after paraquat withdrawal, the level of dopamine in the caudate–putamen was significantly increased, and earlier decreases in DOPAC and HVA in the substantia nigra, as well as [3H]GBR 12,935 binding in the caudate–putamen were reversed. Moreover, an increase in serotonin turnover in the caudate–putamen and prefrontal cortex, and noradrenaline level in the former structure was observed 2–3 days after paraquat withdrawal. Three days after the last paraquat injection 24–35% decreases in the proenkephalin mRNA levels and 5–7% reduction in glutamic acid decarboxylase (GAD)67 mRNA were found in the caudate–putamen. The present study
suggests that subchronic paraquat administration triggers processes characteristic of early stages of dopaminergic neuron degeneration, and activates compensatory mechanisms involving dopaminergic, noradrenergic, serotonergic and GABAergic transmissions.
suggests that subchronic paraquat administration triggers processes characteristic of early stages of dopaminergic neuron degeneration, and activates compensatory mechanisms involving dopaminergic, noradrenergic, serotonergic and GABAergic transmissions.
Research Interests:
Research Interests: Neuroscience, Psychology, Animals, Metabotropic Glutamate Receptors, Male, and 15 moreSubstantia nigra, Synaptic Transmission, Haloperidol, mRna expression levels, Opioid Peptides, Rats, Globus Pallidus, Basal ganglia, Wistar Rats, Neural pathways, Neurosciences, Glutamic Acid, Gene Expression Regulation, Glutamate Receptor, and Dopamine antagonists
The aim of the present study was to find out whether a blockade of adenosine A2A receptors by the selective antagonist, SCH 58261, potentiates the attenuating effect of L-DOPA, the well-known antiparkinsonian drug, on parkinsonian-like... more
The aim of the present study was to find out whether a blockade of adenosine A2A receptors by the selective antagonist, SCH 58261, potentiates the attenuating effect of L-DOPA, the well-known antiparkinsonian drug, on parkinsonian-like muscle rigidity in rats. Muscle tone was examined using a combined mechano- and electromyographic method, which simultaneously measured muscle resistance of a rat hindfoot to passive extension and flexion in the ankle joint and the electromyographic (EMG) activity of the antagonistic muscles of that joint: gastrocnemius and tibialis anterior. Muscle rigidity was produced by reserpine (5 mg/kg ip) injected in combination with alpha-methyl-p-tyrosine (alpha-MT, 250 mg/kg ip). L-DOPA (25 mg/kg ip) or SCH 58261 (0.1 mg/kg ip) administered separately, slightly influenced the reserpine + alpha-MT-induced muscle rigidity. However, only ankle joint extension was affected significantly while the effect on flexion of the rat hindfoot was not significant. Neithe...
Research Interests:
Schizophrenia is a complex neuropsychiatric disorder characterized by cognitive deficits, and positive and negative symptoms. All antipsychotics currently used in clinical practice are dopamine D2 receptor antagonists. The idea that... more
Schizophrenia is a complex neuropsychiatric disorder characterized by cognitive deficits, and positive and negative symptoms. All antipsychotics currently used in clinical practice are dopamine D2 receptor antagonists. The idea that adenosine A2A receptor agonists might be of interest for the treatment of schizophrenia derived from studies showing the existence of antagonistic intramembrane interaction between A2A and D2 receptors. Based on results obtained in animal models, a putative antipsychotic-like profile of A2A agonists was put forward. However, A2A agonists were shown to have detrimental effects in animal models of learning and memory. Moreover, these compounds produce many peripheral side-effects which limits their use in clinical trials. On the other hand, The results concerning the influence of A2A receptor antagonists in animal models used in schizophrenia studies such as locomotor activity and prepulse inhibition are fairly controversial. Some cognitive enhancing properties of A2A receptor antagonists have also been found in rats. Recent results showing the existence of heteromeric A2A/D3 and A2A/mGlu5 receptor complexes seem to open up new perspectives on the search for novel therapies of schizophrenia.
Research Interests:
Research Interests:
Here we aimed to evaluate: (1) Rhes mRNA expression in mouse midbrain, (2) the effect of Rhes deletion on the number of dopamine neurons, (3) nigrostriatal-sensitive behavior during aging in knockout mice. Radioactive in situ... more
Here we aimed to evaluate: (1) Rhes mRNA expression in mouse midbrain, (2) the effect of Rhes deletion on the number of dopamine neurons, (3) nigrostriatal-sensitive behavior during aging in knockout mice. Radioactive in situ hybridization was assessed in adult mice. The beam-walking test was executed in 3-, 6- and 12-month-old mice. Immunohistochemistry of midbrain tyrosine hydroxylase (TH)-positive neurons was performed in 6- and 12-month-old mice. Rhes mRNA is expressed in TH-positive neurons of SNpc and the ventral tegmental area. Moreover, lack of Rhes leads to roughly a 20% loss of nigral TH-positive neurons in both 6- and 12-month-old mutants, when compared with their age-matched controls. Finally, lack of Rhes triggers subtle alterations in motor performance and coordination during aging. Our findings indicate a fine-tuning role of Rhes in regulating the number of TH-positive neurons of the substantia nigra and nigrostriatal-sensitive motor behavior during aging. © 2016 International Parkinson and Movement Disorder Society.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Animal studies have shown that a depletion of dopamine or blockade of dopamine D2 receptors in the striatum produces an increase in striatal proenkephalin (PENK) mRNA expression and an increase in GABAergic transmission in the globus... more
Animal studies have shown that a depletion of dopamine or blockade of dopamine D2 receptors in the striatum produces an increase in striatal proenkephalin (PENK) mRNA expression and an increase in GABAergic transmission in the globus pallidus. Therefore, it has been suggested that an enhanced striatal PENK mRNA expression may reflect to some extent an increase in the activity of the GABAergic striatopallidal pathway whose overactivity has been suggested to take place in the course of Parkinson's disease. Therefore, the aim of the study was to investigate the role of 1,2,3,4-tetrahydroisoquinoline (TIQ), an endogenous substance suspected of producing parkinsonism in humans, in the regulation of the activity of GABAergic striatopallidal pathway in rats. TIQ administered acutely at the dose of 100 mg/kg ip increased the PENK mRNA expression in the dorsal part of the striatum at two levels I and II (rostral and central striatum, respectively). No changes were noticed in the ventral part of the striatum. Moreover, TIQ given chronically to rats for 3 weeks did not modify the level of PENK mRNA in any examined part of the striatum. The present results show that the effect of TIQ on the PENK mRNA expression is different from that described for proparkinsonian model neurotoxins (MPTP, 6-OHDA) as well as for typical neuroleptics, such as haloperidol.
Research Interests:
The aim of the study was to examine the effects of preferential agonists of dopamine D3 receptors: pramipexole and 7-OH-DPAT on the harmaline-induced tremor in rats (a model of essential tremor, ET). To study receptor mechanisms of these... more
The aim of the study was to examine the effects of preferential agonists of dopamine D3 receptors: pramipexole and 7-OH-DPAT on the harmaline-induced tremor in rats (a model of essential tremor, ET). To study receptor mechanisms of these drugs, rats were pretreated with dopamine D3 receptor antagonists-SB-277011-A and SR-21502, an antagonist of presynaptic D2/D3 receptors-amisulpride, or a nonselective antagonist of D2-like receptors, haloperidol, at a postsynaptic dose. For tremor measurement, fully automated force plate actimeters were used and data were analyzed using fast Fourier transform. Harmaline (15 mg/kg ip)-triggered tremor was manifested by an increase in the power within 9-15 Hz band (AP2). Pramipexole administered at a low (0.1 mg/kg sc), but not higher doses (0.3 and 1 mg/kg sc), and 7-OH-DPAT (0.1, 0.3, and 1 mg/kg sc) reversed the harmaline-increased AP2. None of the examined dopamine antagonists: SB-277011-A (10 mg/kg ip), SR-21502 (15 mg/kg ip), haloperidol (0.5 m...
Research Interests:
Previous studies have demonstrated that caffeine administration to adult mice potentiates glial activation induced by 3,4-methylenedioxymethamphetamine (MDMA). Since neuroinflammatory response seems to correlate with neurodegeneration,... more
Previous studies have demonstrated that caffeine administration to adult mice potentiates glial activation induced by 3,4-methylenedioxymethamphetamine (MDMA). Since neuroinflammatory response seems to correlate with neurodegeneration, and the young brain is particularly vulnerable to neurotoxicity, we evaluated dopamine neuron degeneration and glial activation in the caudate-putamen (CPu) and substantia nigra pars compacta (SNc) of adolescent and adult mice. Mice were treated with MDMA (4×20 mg/kg), alone or with caffeine (10 mg/kg). Interleukin (IL)-1β, tumor necrosis factor (TNF)-α, neuronal nitric oxide synthase (nNOS) were evaluated in CPu, whereas tyrosine hydroxylase (TH), glial fibrillary-acidic protein (GFAP) and CD11b were evaluated in CPu and SNc by immunohistochemistry. MDMA decreased TH in SNc of both adolescent and adult mice, whereas TH-positive fibers in CPu were only decreased in adults. In CPu of adolescent mice, caffeine potentiated MDMA-induced GFAP without alter...
Research Interests: Aging, Neurochemistry, Inflammation, Caffeine, Mice, and 5 moreAnimals, Male, Age Factors, Neurosciences, and Dopaminergic Neurons
The aim of the present study was to find out whether blockade of adenosine A2A receptors by a selective antagonist, SCH 58261, influenced parkinsonian-like muscle rigidity. Muscle tone was examined using a combined mechano- and... more
The aim of the present study was to find out whether blockade of adenosine A2A receptors by a selective antagonist, SCH 58261, influenced parkinsonian-like muscle rigidity. Muscle tone was examined using a combined mechano- and electromyographic method which simultaneously measured muscle resistance (MMG) of a rat hindfoot to passive extension and flexion in the ankle joint and electromyographic activity (EMG) of the antagonistic muscles of that joint: gastrocnemius and tibialis anterior. Muscle rigidity produced by reserpine (5 mg/kg + α-methyl-p-tyrosine, 250 mg/kg) was antagonized by SCH 58261 (0.1–5 mg/kg). SCH 58261 (5 mg/kg) also reduced reserpine-enhanced tonic and reflex EMG activities in both the gastrocnemius and the tibialis muscles. Moreover, SCH 58261 in doses of 1 and 5 mg/kg abolished muscle resistance induced by haloperidol (0.5 mg/kg). However, only the highest dose of SCH 58261 (5 mg/kg) decreased tonic EMG activity enhanced by haloperidol. Administration of L-DOPA (75 and 100 mg/kg) dose-dependently decreased the muscle resistance as well as tonic EMG activity evoked by haloperidol. Combined administration of SCH 58261 (0.1 mg/kg) and L-DOPA (50 mg/kg) in doses which did not affect the haloperidol-induced muscle rigidity produced a pronounced synergistic effect. The ability of SCH 58261 to diminish the parkinsonian-like muscle rigidity and to potentiate the effect of L-DOPA in this model seems to indicate a therapeutic value of this compound in the treatment of Parkinson's disease. Synapse 41:160–171, 2001. © 2001 Wiley-Liss, Inc.
Research Interests:
Research Interests:
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,... more
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.
Research Interests: Glutamate, Cerebral Cortex, Animals, Male, Rats, and 4 moreNMDA Receptors, Seizures, Glycine, and Bicuculline
Research Interests:
Research Interests:
Research Interests:
Harmaline is a β-carboline derivative which is commonly used for modelling one of the most frequent movement disorder, essential tremor (ET), in animals and screening potential tremorolytic drugs. Oscillation frequency of the... more
Harmaline is a β-carboline derivative which is commonly used for modelling one of the most frequent movement disorder, essential tremor (ET), in animals and screening potential tremorolytic drugs. Oscillation frequency of the harmaline-induced kinetic/postural tremor is 10-12 Hz in rats. It is generally accepted that the primary cause of tremor induced by this compound is abnormal synchronous activation of the olivo-cerebellar glutamatergic climbing fibres. This activation leads to increased glutamate release in the cerebellum and induction of complex spike activity of Purkinje cells of the cerebellar cortex. However, mechanisms underlying harmaline-induced tremor seem to involve also other neurotransmitter systems. The aim of the present study was to examine the influence of the non-selective agonists of dopamine receptors: apomorphine (D1 – D5) and pramipexole (D2, D3) on the harmaline-induced tremor in rats. Propranolol (the first-line treatment of ET) was used as a reference com...
An involvement of glutamatergic transmission in schizophrenia has been postulated for several years. According to that view, hypofunction of NMDA receptors and a compensatory increase in glutamate release which overstimulates non-NMDA... more
An involvement of glutamatergic transmission in schizophrenia has been postulated for several years. According to that view, hypofunction of NMDA receptors and a compensatory increase in glutamate release which overstimulates non-NMDA receptors contributes to psychotic symptoms. Therefore, potential antipsychotic drugs are searched for among compounds which block AMPA receptors and inhibit glutamate release. (R,S)-3,4-dicarboxyphenylglycine [(R,S)-3,4-DCPG] is a mixed antagonist of AMPA receptors and agonist of an autoreceptor, i.e. metabotropic glutamate receptor 8. The aim of the study was to look for putative antipsychotic properties of (R,S)-3,4-DCPG in the model of locomotor stimulation induced by amphetamine or phencyclidine in mice. Moreover, a risk of extrapyramidal side-effects induced by this compound was examined, as capability to induce catalepsy in the bar test and to increase the proenkephalin mRNA expression, measured autoradiographically in striatal slices by in situ...
Research Interests: Polish, Drug interactions, Mice, Animals, Male, and 4 moreAmphetamine, Phencyclidine, Glycine, and Motor activity
The aim of the present study was to examine the influence of 3-month administration of the typical neuroleptic haloperidol (1 mg/kg/day) and the atypical one clozapine (30 mg/kg/day) on the expression of the NMDA-R1 mRNA in different... more
The aim of the present study was to examine the influence of 3-month administration of the typical neuroleptic haloperidol (1 mg/kg/day) and the atypical one clozapine (30 mg/kg/day) on the expression of the NMDA-R1 mRNA in different brain structures using in situ hybridization in rats. A long-term treatment with haloperidol decreased the NMDA-R1 mRNA level in intermediate and caudal parts of the caudate-putamen and in more caudally localized regions of parietal and frontal cortices, but increased it in the CA1 region of the hippocampus. No significant changes in the nucleus accumbens, insular cortex, CA3 and dentate gyrus of the hippocampus were found after haloperidol administration. Clozapine did not influence the NMDA-R1 mRNA expression in the hippocampus, as well as in the intermediate and caudal regions of the caudate-putamen, but significantly increased it in the rostral region of the latter structure, in the nucleus accumbens and insular cortex. The present study suggests th...
Research Interests: Polish, In Situ Hybridization, Brain, Animals, Male, and 5 moreRat Brain, Haloperidol, Rats, Wistar Rats, and Clozapine
The aim of this study was to examine the role of cortical NMDA receptors in the antipsychotic action of neuroleptics. Haloperidol (1 mg/kg/day) and clozapine (30 mg/kg/day) were administered to rats in drinking water. Autoradiographic and... more
The aim of this study was to examine the role of cortical NMDA receptors in the antipsychotic action of neuroleptics. Haloperidol (1 mg/kg/day) and clozapine (30 mg/kg/day) were administered to rats in drinking water. Autoradiographic and saturation binding analyses showed that a 3-month treatment with both haloperidol and clozapine increased the density of NMDA receptors labelled with [3H]CGP 39653 (a competitive antagonist) in the parietal and insular cortices. Haloperidol additionally increased the binding of that ligand in the frontal cortex. None of those neuroleptics influenced the binding of [3H]MK-801, an uncompetitive antagonist of NMDA receptors, in the frontal, parietal or insular cortices. A 6-week and a 3-month treatment with haloperidol antagonized the deficit of prepulse inhibition induced by phencyclidine (5 mg/kg s.c.). In contrast, short-term (4-day) administration of that neuroleptic was ineffective. The present study suggests that the increased density of cortica...
Research Interests:
Selective toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a parkinsonism inducing compound, is well known to be related to an uptake of its active metabolite MPP+ into dopaminergic neurons by dopamine transporter (DAT).... more
Selective toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a parkinsonism inducing compound, is well known to be related to an uptake of its active metabolite MPP+ into dopaminergic neurons by dopamine transporter (DAT). The aim of the present study was to examine whether paraquat, a commonly used herbicide, which is an 1-methyl-4-phenyl-pyridinium ion (MPP+) analogue, affects DAT in vivo in rats. Paraquat administered at a dose of 10 mg/kg ip decreased the binding of [3H]GBR 12,935 to DAT measured by quantitative autoradiography in the dorsal and ventral caudate-putamen, but not in the substantia nigra pars compacta. Moreover, this compound increased the level of 3-methoxytyramine (3-MT) and 3-MT/dopamine ratio in the anterior and posterior caudate-putamen measured by HPLC with electrochemical detection. No other alterations in the levels of dopamine and its metabolites were found in the caudate-putamen and substantia nigra. The present study seems to suggest that s...
Research Interests: Dopamine, Animals, Male, Substantia nigra, Paraquat, and 4 moreHerbicides, Rats, Wistar Rats, and Pharmacological
Harmaline-induced tremor is a well-known model of essential tremor in humans. The aim of the present study was to examine the influence of apomorphine, a non-selective dopamine receptor agonist, on the tremor induced by harmaline in rats.... more
Harmaline-induced tremor is a well-known model of essential tremor in humans. The aim of the present study was to examine the influence of apomorphine, a non-selective dopamine receptor agonist, on the tremor induced by harmaline in rats. Propranolol (a first-line drug in essential tremor) was used as a reference compound. Tremor, locomotor activity and focused stereotypy were measured objectively using force plate actimeters. Tremor was analyzed using a Fourier transform to generate power spectra for rhythmic behavior. The tremor induced by harmaline administered at a dose of 15 mg/kg ip was associated with an increase in power in the 9-15 Hz band (AP2) and in the tremor index, calculated as a difference between AP2 and power in the 0-8 Hz band (AP1). Propranolol injected at a dose of 20mg/kg ip reversed both of these effects of harmaline. Apomorphine administered at the doses of 0.5 and 1mg/kg sc further enhanced AP2 and at the lower dose also the tremor index elevated by harmaline. This increase in AP2 was stronger than enhancement of locomotor activity induced by apomorphine in the harmaline-treated animals. The present study suggests that the dopamine agonist apomorphine enhances the tremor induced by harmaline, and this effect is at least partly independent of hyperactivity.
Research Interests:
The aim of this paper was to investigate whether rotenone, a pesticide causing experimental parkinsonism, causes direct damage to dopaminergic structure when injected intracerebrally and whether this action may be prevented by peripheral... more
The aim of this paper was to investigate whether rotenone, a pesticide causing experimental parkinsonism, causes direct damage to dopaminergic structure when injected intracerebrally and whether this action may be prevented by peripheral administration of 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ), an endogenous compound with anti-dopaminergic activity. Male Wistar rats were injected unilaterally into the median forebrain bundle with 2 microg rotenone, and received 1MeTIQ, 50 mg/kg i.p. 1 h before and then daily for 21 d. To compare the effect of intracerebral and peripheral treatment, rotenone was also given once or for 7 d in a dose of 10 mg/kg s.c. Dopamine, serotonin and their metabolites were assessed by HPLC in the substantia nigra and striatum. While a single subcutaneous rotenone dose did not produce any change in striatal dopamine metabolism, the multiple treatments resulted in changes suggesting a shift in the metabolism towards oxidative desamination and reduction o...
Research Interests:
The aim of the present study was to evaluate age-related changes in NMDA and AMPA receptors in old female rats. To this end a quantitative autoradiography of [3H]-MK-801 and [3H]-AMPA binding was performed in the brain of young... more
The aim of the present study was to evaluate age-related changes in NMDA and AMPA receptors in old female rats. To this end a quantitative autoradiography of [3H]-MK-801 and [3H]-AMPA binding was performed in the brain of young (3-month-old), middle-aged (12-month-old) and old (36-month-old) rats. Moreover, the binding of [3H]-spiperone to D2 dopamine receptors was also examined. No changes were observed in the binding of [3H]-MK-801 or [3H]-AMPA in middle-aged rats compared to young ones. In the caudate-putamen and shell and core of the nucleus accumbens septi of old rats, a pronounced decrease in the [3H]-MK-801 binding and a decreasing tendency in the [3H]-AMPA binding were observed. Furthermore, the binding of [3H]-MK-801 and [3H]-AMPA was reduced in the hippocampal formation and, additionally, a marked decline in the [3H]-MK-801 binding in different parts of the cerebral cortex including the frontal, parietal, cingulate, pyriform and insular cortices was found. The [3H]-spipero...
Research Interests:
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... more
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.