A. Pilc | Jagiellonian University (original) (raw)
Papers by A. Pilc
European Neuropsychopharmacology, 2013
Naunyn-Schmiedeberg's Archives of Pharmacology, 2000
Evidence suggests that metabotropic glutamate receptors (mGluR) are involved in mediating seizure... more Evidence suggests that metabotropic glutamate receptors (mGluR) are involved in mediating seizures and epileptogenesis. In the present experiments, the selective, group II mGluR agonist (+)-2-aminobicyclo-[3.1.0]hexane-2,6-dicarboxylic acid (LY354740, 0.1-1.0 microM) inhibited spontaneous epileptiform discharges which developed in rat cortical slices in Mg2+-free medium. LY354740 (4-16 mg/kg) administered prior to an injection of pentylenetetrazol (80 mg/kg) or picrotoxin (3.2 mg/kg) produced a dose-dependent decrease in the number of mice exhibiting clonic convulsions, but had no effect on N-methyl-D-aspartate (NMDA, 150 mg/kg)-induced convulsions. LY354740 (4-16 mg/kg) did not affect lethality induced in mice by pentylenetetrazol, picrotoxin or NMDA. LY354740 potentiated the anticonvulsant activity of the conventional antiepileptic drug diazepam, significantly decreasing the ED50 for that drug's effect on pentylenetetrazol-induced convulsions by 30%, but had no influence on anticonvulsant activity of ethosuximide and valproic acid. A pharmacokinetic interaction between LY354740 and diazepam, leading to the lowering of the plasma level of free diazepam, was also demonstrated. Our data suggest that the group II mGluR agonist LY354740 possesses anti-seizure activity and may modify the effects of some conventional antiepileptic drugs.
![Research paper thumbnail of The influence of electroshock on adrenoceptor function in rat brain cerebral cortex: selectivity for the [alpha]-adrenoceptor site](https://attachments.academia-assets.com/68330734/thumbnails/1.jpg)
](European journal of …, 1988
The present study was undertaken to examine the effect of electroshock on adrenoceptor-mediated c... more The present study was undertaken to examine the effect of electroshock on adrenoceptor-mediated cAMP and inositol phosphate accumulation in rat brain cerebral cortical slices. Under the conditions of these experiments, isoproterenol-induced cAMP accumulation was unaltered by electroshock, although there was a significant reduction in the norepinephrine-and isoproterenol + 6-fluoronorepinephrine-stimulated responses. No change in a-adrenoceptor-mediated inositol phosphate accumulation was noted. The results indicate that electroshock selectively modifies an a-adrenoceptor system in brain that differs from that associated with inositol phosphate accumulation.
P5. Addiction in the abstinent rats at 10 h. On the last day of ethanol ingestion the levels of n... more P5. Addiction in the abstinent rats at 10 h. On the last day of ethanol ingestion the levels of norharman were significantly elevated (0.224-0.05 nmol/l, mean+SEM, n=8) compared to control rats (0.064-0.01 nmol/l, n=9), whereas at 10 h postwithdrawal these levels were significantly reduced compared to zero time (0.114-0.01, n=18). The norharman levels in the livers of the three groups showed a similar pattern. It was also found that the capacity of the liver of the alcohol-dependent rats to catabolize norharman was reduced compared to the control rats. Moreover, norharman attenuated the behavioural signs of alcohol withdrawal significantly (p=0.0002) and had no effect on normal behaviour. Conclusion: Our results clearly show that forced ethanol ingestion increases the plasma and liver levels of norharman in rats, while these levels sharply decreased to nearly control levels 10 h after withdrawal. This is also the time point at which the severest withdrawal signs were observed. Moreover, the beta-carboline norharman was able to attenuate these signs. The mechanism behind the increased norharman levels in alcohol-dependent rats may be inhibition of the synthesis and/or activity of the enzyme(s) responsible for the breakdown of norharman.
Behavioural pharmacology, Sep 1, 2008
We describe the anxiolytic-like effects of the first, selective metabotropic G-protein-coupled gl... more We describe the anxiolytic-like effects of the first, selective metabotropic G-protein-coupled glutamate 7 (mGlu7) receptor agonist, N, N′-dibenzyhydryl-ethane-1, 2-diamine dihydrochloride (AMN082), as measured in the modified stress-induced hyperthermia (SIH) and the four-plate tests. Administration of AMN082 (3-6 mg/kg intraperitoneally) to Swiss mice produced anxiolytic-like effects in the modified SIH and four-plate tests. Moreover, it was ineffective as an anxiolytic in the SIH test in mGlu7 receptor knockout mice as ...
Behavioural pharmacology, Sep 1, 2008
We describe the anxiolytic-like effects of the first, selective metabotropic G-protein-coupled gl... more We describe the anxiolytic-like effects of the first, selective metabotropic G-protein-coupled glutamate 7 (mGlu7) receptor agonist, N, N′-dibenzyhydryl-ethane-1, 2-diamine dihydrochloride (AMN082), as measured in the modified stress-induced hyperthermia (SIH) and the four-plate tests. Administration of AMN082 (3-6 mg/kg intraperitoneally) to Swiss mice produced anxiolytic-like effects in the modified SIH and four-plate tests. Moreover, it was ineffective as an anxiolytic in the SIH test in mGlu7 receptor knockout mice as ...
Behavioural Pharmacology, 2005
Acta physiologica Polonica
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2010
It is well documented that physical activity can induce a number of various stimuli which are abl... more It is well documented that physical activity can induce a number of various stimuli which are able to enhance the strength and endurance performance of muscles. Moreover, regular physical activity can preserve or delay the appearance of several metabolic disorders in the human body. Physical exercise is also known to enhance the mood and cognitive functions of active people, although the physiological backgrounds of these effects remain unclear. In recent years, since the pioneering study in the past showed that physical activity increases the expression of the brain derived neurothophic factor (BDNF) in the rat brain, a number of studies were undertaken in order to establish the link between that neurothrophin and post-exercise enhancement of mood and cognitive functions in humans. It was recently demonstrated that physical exercise can increase plasma and/or serum BDNF concentration in humans. It was also reported that physical exercise or electrical stimulation can increase the B...
Pharmacological reports : PR
Olfactory bulbectomy (OB) is an established animal model of depression that has been investigated... more Olfactory bulbectomy (OB) is an established animal model of depression that has been investigated mostly in rats. As in human major depression, OB induces behavioral alterations that can be ameliorated by chronic antidepressant treatment. Furthermore, it was shown that OB induces changes of various protein receptor levels in brain areas that are important in antidepressant therapy. In the present study, we investigated the effects of OB and amitriptyline (AMI) treatment on the expression of metabotropic glutamate receptors (mGluR) in the mouse hippocampus using the western blot method. AMI was given for 14 days, in a dose of 10 mg/kg, intraperitoneally. The levels of most subtypes of mGlu receptors, e.g., mGlu1a (mGluR group I), mGlu2/3 (mGluR group II), mGlu4, and mGlu7 (mGluR group III) receptors, were measured. Additionally, immunohistochemical stainings were made in slices of the mouse hippocampus. It was found that OB induced an increase in mGluR1a-immunoreactivity (IR), which ...
Pharmacological reports : PR
Substances acting as agonists of group III mGlu receptors were shown to induce an antianxiety-lik... more Substances acting as agonists of group III mGlu receptors were shown to induce an antianxiety-like effect after intrahippocampal administration to rats. The purpose of the present study was to establish whether the selective mGlu8 receptor agonist (S)-3,4-dicarboxyphenylglycine ((S)-3,4-DCPG) induced an anxiolytic-like effect after injection into the basolateral amygdala nuclei or the CA1 region of the hippocampus in the conflict drinking Vogel test in rats. The obtained results indicate that (S)-3,4-DCPG (10, 50 and 100 nmol/rat) produces no anticonflict effect in rats. We conclude that selective stimulation of mGlu8 receptors (a subtype of group III mGluRs) does not evoke anxiolytic-like activity, and that the mGlu8 receptors are of no significance for anxiolytic-like effects of group III mGluR agonists.
Pharmacological reports : PR
The antidepressant-like activity of magnesium, the non-specific N-methyl-D-aspartate glutamate re... more The antidepressant-like activity of magnesium, the non-specific N-methyl-D-aspartate glutamate receptor antagonist, in the mice forced swim test was demonstrated previously. In the present study, the effects of this biometal were studied in the rat forced swim test. Magnesium (MgCl2) at doses ranging from 15 to 50 mg Mg/kg reduced the immobility time in the forced swim test, thus exerting antidepressant-like activity. To evaluate tolerance to this effect, we also performed experiments with the following acute/chronic magnesium treatment schedule: chronic saline and saline challenge at 0.5 h before behavioral experiments (S + S), chronic saline and magnesium challenge (S + Mg), chronic magnesium and saline challenge (Mg + S), chronic magnesium and magnesium challenge (Mg + Mg). The antidepressant-like effect of magnesium was demonstrated in the group treated acutely with magnesium (S + Mg) but not in the chronically treated group (Mg + S) and (Mg + Mg). It is interesting to note that...
Current opinion in investigational drugs (London, England : 2000), 2001
The glutamatergic system has received considerable attention over recent years as a potential tar... more The glutamatergic system has received considerable attention over recent years as a potential target for anxiolytic drugs. In spite of the pronounced anxiolytic-like effects of competitive and non-competitive antagonists of NMDA receptors in animal models of anxiety, these substances can not be regarded as potential anxiolytic drugs, mainly due to their side-effect profiles (eg, ataxia, myorelaxation, impairment of learning and memory processes and psychotomimetic effects). Antagonists and partial agonists of the glycine, receptor inhibit function of the NMDA receptor complex and evoke in animals an anxiolytic-like response. Although data concerning anti-anxiety-like effects of glycine, receptor antagonists are not very promising, studies are underway to develop new, brain-penetrating agents devoid of side effects. Further developments are necessary to more fully elucidate the possible involvement of AMPA/kainate receptors in anxiety. The recent discovery of metabotropic glutamate r...
Psychiatria polska
This article presents a review of the interactions between zinc and glutamate system in the patho... more This article presents a review of the interactions between zinc and glutamate system in the pathophysiology and treatment of depression.
Polish journal of pharmacology
There are several data indicating the involvement of metabotropic glutamate receptors (mGluR) in ... more There are several data indicating the involvement of metabotropic glutamate receptors (mGluR) in seizures and epileptogenesis. In the present experiments, the selective group II mGluR agonist (+)-2-aminobicyclo-[3.1.0]hexane-2,6-dicarboxylic acid (LY 354740) at doses from 4 to 16 mg/kg) administered prior to the injection of pentetrazole (80 mg/kg) or picrotoxin (3.2 mg/kg) produced a dose-dependent decrease in the number of mice exhibiting clonic convulsions. Our data suggest that group II mGluR agonist LY 354740 possesses antiseizure activity.
Polish journal of pharmacology
The existence of multiple metabotropic receptors for excitatory amino acids is firmly established... more The existence of multiple metabotropic receptors for excitatory amino acids is firmly established by recent cloning experiments. Several subtypes of those receptors are coupled to adenylate cyclase. (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R)-ACPD) is a selective agonist for metabotropic glutamate receptors, it influences cyclic AMP accumulation in brain and is able to enhance the effect of other substances which stimulate cyclic AMP accumulation. Here we present data showing that (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid enhanced the action of noradrenaline on cyclic AMP accumulation in rat brain cortical slices (EC50 40 microM). On the contrary, it inhibited the action of noradrenaline in primary glial cell cultures (EC50 50 microM), being without any effect on noradrenaline-induced cyclic AMP accumulation in primary neuronal cell cultures. The differences may reflect stimulation of different types of metabotropic glutamate receptors in various preparations f...
The Journal of clinical psychiatry, 1982
Most published data on histamine skin tests on schizophrenic patients show them to be insensitive... more Most published data on histamine skin tests on schizophrenic patients show them to be insensitive relative to normals or other psychotic patients. However, experimental conditions have varied and in most cases only a single dose of histamine was used. We have compared 13 volunteer controls and 16 paranoid schizophrenics; each subject was injected intradermally with histamine, 10, 20, and 50 microgram, doses predetermined in volunteers to give a dose-response curve. Wheal and flare were measured at 10 and 20 minutes, intervals near the time of maximum flare. We found no statistically significant differences between normal controls and schizophrenic patients.
European Neuropsychopharmacology, 2013
Naunyn-Schmiedeberg's Archives of Pharmacology, 2000
Evidence suggests that metabotropic glutamate receptors (mGluR) are involved in mediating seizure... more Evidence suggests that metabotropic glutamate receptors (mGluR) are involved in mediating seizures and epileptogenesis. In the present experiments, the selective, group II mGluR agonist (+)-2-aminobicyclo-[3.1.0]hexane-2,6-dicarboxylic acid (LY354740, 0.1-1.0 microM) inhibited spontaneous epileptiform discharges which developed in rat cortical slices in Mg2+-free medium. LY354740 (4-16 mg/kg) administered prior to an injection of pentylenetetrazol (80 mg/kg) or picrotoxin (3.2 mg/kg) produced a dose-dependent decrease in the number of mice exhibiting clonic convulsions, but had no effect on N-methyl-D-aspartate (NMDA, 150 mg/kg)-induced convulsions. LY354740 (4-16 mg/kg) did not affect lethality induced in mice by pentylenetetrazol, picrotoxin or NMDA. LY354740 potentiated the anticonvulsant activity of the conventional antiepileptic drug diazepam, significantly decreasing the ED50 for that drug's effect on pentylenetetrazol-induced convulsions by 30%, but had no influence on anticonvulsant activity of ethosuximide and valproic acid. A pharmacokinetic interaction between LY354740 and diazepam, leading to the lowering of the plasma level of free diazepam, was also demonstrated. Our data suggest that the group II mGluR agonist LY354740 possesses anti-seizure activity and may modify the effects of some conventional antiepileptic drugs.
European journal of …, 1988
The present study was undertaken to examine the effect of electroshock on adrenoceptor-mediated c... more The present study was undertaken to examine the effect of electroshock on adrenoceptor-mediated cAMP and inositol phosphate accumulation in rat brain cerebral cortical slices. Under the conditions of these experiments, isoproterenol-induced cAMP accumulation was unaltered by electroshock, although there was a significant reduction in the norepinephrine-and isoproterenol + 6-fluoronorepinephrine-stimulated responses. No change in a-adrenoceptor-mediated inositol phosphate accumulation was noted. The results indicate that electroshock selectively modifies an a-adrenoceptor system in brain that differs from that associated with inositol phosphate accumulation.
P5. Addiction in the abstinent rats at 10 h. On the last day of ethanol ingestion the levels of n... more P5. Addiction in the abstinent rats at 10 h. On the last day of ethanol ingestion the levels of norharman were significantly elevated (0.224-0.05 nmol/l, mean+SEM, n=8) compared to control rats (0.064-0.01 nmol/l, n=9), whereas at 10 h postwithdrawal these levels were significantly reduced compared to zero time (0.114-0.01, n=18). The norharman levels in the livers of the three groups showed a similar pattern. It was also found that the capacity of the liver of the alcohol-dependent rats to catabolize norharman was reduced compared to the control rats. Moreover, norharman attenuated the behavioural signs of alcohol withdrawal significantly (p=0.0002) and had no effect on normal behaviour. Conclusion: Our results clearly show that forced ethanol ingestion increases the plasma and liver levels of norharman in rats, while these levels sharply decreased to nearly control levels 10 h after withdrawal. This is also the time point at which the severest withdrawal signs were observed. Moreover, the beta-carboline norharman was able to attenuate these signs. The mechanism behind the increased norharman levels in alcohol-dependent rats may be inhibition of the synthesis and/or activity of the enzyme(s) responsible for the breakdown of norharman.
Behavioural pharmacology, Sep 1, 2008
We describe the anxiolytic-like effects of the first, selective metabotropic G-protein-coupled gl... more We describe the anxiolytic-like effects of the first, selective metabotropic G-protein-coupled glutamate 7 (mGlu7) receptor agonist, N, N′-dibenzyhydryl-ethane-1, 2-diamine dihydrochloride (AMN082), as measured in the modified stress-induced hyperthermia (SIH) and the four-plate tests. Administration of AMN082 (3-6 mg/kg intraperitoneally) to Swiss mice produced anxiolytic-like effects in the modified SIH and four-plate tests. Moreover, it was ineffective as an anxiolytic in the SIH test in mGlu7 receptor knockout mice as ...
Behavioural pharmacology, Sep 1, 2008
We describe the anxiolytic-like effects of the first, selective metabotropic G-protein-coupled gl... more We describe the anxiolytic-like effects of the first, selective metabotropic G-protein-coupled glutamate 7 (mGlu7) receptor agonist, N, N′-dibenzyhydryl-ethane-1, 2-diamine dihydrochloride (AMN082), as measured in the modified stress-induced hyperthermia (SIH) and the four-plate tests. Administration of AMN082 (3-6 mg/kg intraperitoneally) to Swiss mice produced anxiolytic-like effects in the modified SIH and four-plate tests. Moreover, it was ineffective as an anxiolytic in the SIH test in mGlu7 receptor knockout mice as ...
Behavioural Pharmacology, 2005
Acta physiologica Polonica
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2010
It is well documented that physical activity can induce a number of various stimuli which are abl... more It is well documented that physical activity can induce a number of various stimuli which are able to enhance the strength and endurance performance of muscles. Moreover, regular physical activity can preserve or delay the appearance of several metabolic disorders in the human body. Physical exercise is also known to enhance the mood and cognitive functions of active people, although the physiological backgrounds of these effects remain unclear. In recent years, since the pioneering study in the past showed that physical activity increases the expression of the brain derived neurothophic factor (BDNF) in the rat brain, a number of studies were undertaken in order to establish the link between that neurothrophin and post-exercise enhancement of mood and cognitive functions in humans. It was recently demonstrated that physical exercise can increase plasma and/or serum BDNF concentration in humans. It was also reported that physical exercise or electrical stimulation can increase the B...
Pharmacological reports : PR
Olfactory bulbectomy (OB) is an established animal model of depression that has been investigated... more Olfactory bulbectomy (OB) is an established animal model of depression that has been investigated mostly in rats. As in human major depression, OB induces behavioral alterations that can be ameliorated by chronic antidepressant treatment. Furthermore, it was shown that OB induces changes of various protein receptor levels in brain areas that are important in antidepressant therapy. In the present study, we investigated the effects of OB and amitriptyline (AMI) treatment on the expression of metabotropic glutamate receptors (mGluR) in the mouse hippocampus using the western blot method. AMI was given for 14 days, in a dose of 10 mg/kg, intraperitoneally. The levels of most subtypes of mGlu receptors, e.g., mGlu1a (mGluR group I), mGlu2/3 (mGluR group II), mGlu4, and mGlu7 (mGluR group III) receptors, were measured. Additionally, immunohistochemical stainings were made in slices of the mouse hippocampus. It was found that OB induced an increase in mGluR1a-immunoreactivity (IR), which ...
Pharmacological reports : PR
Substances acting as agonists of group III mGlu receptors were shown to induce an antianxiety-lik... more Substances acting as agonists of group III mGlu receptors were shown to induce an antianxiety-like effect after intrahippocampal administration to rats. The purpose of the present study was to establish whether the selective mGlu8 receptor agonist (S)-3,4-dicarboxyphenylglycine ((S)-3,4-DCPG) induced an anxiolytic-like effect after injection into the basolateral amygdala nuclei or the CA1 region of the hippocampus in the conflict drinking Vogel test in rats. The obtained results indicate that (S)-3,4-DCPG (10, 50 and 100 nmol/rat) produces no anticonflict effect in rats. We conclude that selective stimulation of mGlu8 receptors (a subtype of group III mGluRs) does not evoke anxiolytic-like activity, and that the mGlu8 receptors are of no significance for anxiolytic-like effects of group III mGluR agonists.
Pharmacological reports : PR
The antidepressant-like activity of magnesium, the non-specific N-methyl-D-aspartate glutamate re... more The antidepressant-like activity of magnesium, the non-specific N-methyl-D-aspartate glutamate receptor antagonist, in the mice forced swim test was demonstrated previously. In the present study, the effects of this biometal were studied in the rat forced swim test. Magnesium (MgCl2) at doses ranging from 15 to 50 mg Mg/kg reduced the immobility time in the forced swim test, thus exerting antidepressant-like activity. To evaluate tolerance to this effect, we also performed experiments with the following acute/chronic magnesium treatment schedule: chronic saline and saline challenge at 0.5 h before behavioral experiments (S + S), chronic saline and magnesium challenge (S + Mg), chronic magnesium and saline challenge (Mg + S), chronic magnesium and magnesium challenge (Mg + Mg). The antidepressant-like effect of magnesium was demonstrated in the group treated acutely with magnesium (S + Mg) but not in the chronically treated group (Mg + S) and (Mg + Mg). It is interesting to note that...
Current opinion in investigational drugs (London, England : 2000), 2001
The glutamatergic system has received considerable attention over recent years as a potential tar... more The glutamatergic system has received considerable attention over recent years as a potential target for anxiolytic drugs. In spite of the pronounced anxiolytic-like effects of competitive and non-competitive antagonists of NMDA receptors in animal models of anxiety, these substances can not be regarded as potential anxiolytic drugs, mainly due to their side-effect profiles (eg, ataxia, myorelaxation, impairment of learning and memory processes and psychotomimetic effects). Antagonists and partial agonists of the glycine, receptor inhibit function of the NMDA receptor complex and evoke in animals an anxiolytic-like response. Although data concerning anti-anxiety-like effects of glycine, receptor antagonists are not very promising, studies are underway to develop new, brain-penetrating agents devoid of side effects. Further developments are necessary to more fully elucidate the possible involvement of AMPA/kainate receptors in anxiety. The recent discovery of metabotropic glutamate r...
Psychiatria polska
This article presents a review of the interactions between zinc and glutamate system in the patho... more This article presents a review of the interactions between zinc and glutamate system in the pathophysiology and treatment of depression.
Polish journal of pharmacology
There are several data indicating the involvement of metabotropic glutamate receptors (mGluR) in ... more There are several data indicating the involvement of metabotropic glutamate receptors (mGluR) in seizures and epileptogenesis. In the present experiments, the selective group II mGluR agonist (+)-2-aminobicyclo-[3.1.0]hexane-2,6-dicarboxylic acid (LY 354740) at doses from 4 to 16 mg/kg) administered prior to the injection of pentetrazole (80 mg/kg) or picrotoxin (3.2 mg/kg) produced a dose-dependent decrease in the number of mice exhibiting clonic convulsions. Our data suggest that group II mGluR agonist LY 354740 possesses antiseizure activity.
Polish journal of pharmacology
The existence of multiple metabotropic receptors for excitatory amino acids is firmly established... more The existence of multiple metabotropic receptors for excitatory amino acids is firmly established by recent cloning experiments. Several subtypes of those receptors are coupled to adenylate cyclase. (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R)-ACPD) is a selective agonist for metabotropic glutamate receptors, it influences cyclic AMP accumulation in brain and is able to enhance the effect of other substances which stimulate cyclic AMP accumulation. Here we present data showing that (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid enhanced the action of noradrenaline on cyclic AMP accumulation in rat brain cortical slices (EC50 40 microM). On the contrary, it inhibited the action of noradrenaline in primary glial cell cultures (EC50 50 microM), being without any effect on noradrenaline-induced cyclic AMP accumulation in primary neuronal cell cultures. The differences may reflect stimulation of different types of metabotropic glutamate receptors in various preparations f...
The Journal of clinical psychiatry, 1982
Most published data on histamine skin tests on schizophrenic patients show them to be insensitive... more Most published data on histamine skin tests on schizophrenic patients show them to be insensitive relative to normals or other psychotic patients. However, experimental conditions have varied and in most cases only a single dose of histamine was used. We have compared 13 volunteer controls and 16 paranoid schizophrenics; each subject was injected intradermally with histamine, 10, 20, and 50 microgram, doses predetermined in volunteers to give a dose-response curve. Wheal and flare were measured at 10 and 20 minutes, intervals near the time of maximum flare. We found no statistically significant differences between normal controls and schizophrenic patients.