Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2001
Pokk Paavo and Marika V~ili: Small platform stress increases exploratory activity of mice in stai... more Pokk Paavo and Marika V~ili: Small platform stress increases exploratory activity of mice in staircase test.
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2004
The aim of the work was to study the effects of litter and the nitric oxide synthase (NOS) inhibi... more The aim of the work was to study the effects of litter and the nitric oxide synthase (NOS) inhibitor N G -nitro-l-arginine (l-NOARG) on the behaviour of mice after acute and chronic ethanol administration and withdrawal. Male outbred NIH/S mice, from 21 litters, were distributed among experimental groups and subjected to acute and chronic ethanol administration. After acute or chronic ethanol administration, the effects of l-NOARG on the behaviour of mice in the plus-maze test were studied. Acute ethanol (1 g/kg, i.p.), l-NOARG (20 and 40 mg/kg, i.p.) and their combination induced an anxiolytic effect. Furthermore, the values for the representatives of different litters tended to be either above or below the group mean, irrespective of the drug treatment. Chronic ethanol administration (23 days by inhalation) induced an anxiolytic effect and ethanol withdrawal induced an anxiogenic effect in the plus-maze. The administration of l-NOARG (20 mg/ kg, i.p.) induced an anxiolytic effect in control mice and had no effect on ethanol-intoxicated mice, but attenuated the anxiogenic effect of ethanol withdrawal in the plus-maze. However, after chronic ethanol administration and withdrawal, litter had no effect on the behaviour of mice. If the litter is a significant determinant in the behaviour of outbred mice, then the use of information about the litter origin of animals could serve for the purposes of reduction. But only if this information is available from breeders. D
The hepatoprotective effects and pharmacokinetics of trans-resveratrol and hydroxystilbenes of th... more The hepatoprotective effects and pharmacokinetics of trans-resveratrol and hydroxystilbenes of the garden rhubarb (Rheum rhaponticum L., R. rhaponticum) root ethanol extract were studied.
The effect of baclofen on the locomotor activity of control and small-platform-stressed mice was ... more The effect of baclofen on the locomotor activity of control and small-platform-stressed mice was studied. In the small platform technique, mice are forced to stay on small platforms (d= 3.5 cm) surrounded by water for 24 h. Small platform stress increased the locomotor activity of mice in the actometer. Baclofen administered at doses of 0.25, 0.5 and 1.0 mg kg(-1)(i.p.) had no effect on the locomotor activity of control mice. In small-platform-stressed mice, the locomotor depressant effect of baclofen was pronounced, being statistically significant at a dose of 1.0 mg kg(-1). These data suggest that small platform stress induces hypersensitivity of mice to the motor depressant effect of baclofen. On the basis of these data it could be proposed that small platform stress induces changes in the function of GABA(B)receptors and that GABA(B)receptors participate in the behavioural changes caused by small platform stress.
The effects of flumazenil, Ro 15-4513 and &bgr;-CCM in the staircase test wer... more The effects of flumazenil, Ro 15-4513 and &bgr;-CCM in the staircase test were studied in control and small platform (SP) stressed mice. SP stress was induced by placing mice on small platforms (3.5 cm in diameter) surrounded by water for 24 h. This model contains several factors of stress, such as rapid eye movement sleep deprivation, isolation, immobilization and falling
Small platform stress was induced in male BALB/c mice by placing them on small platforms (d = 3.5... more Small platform stress was induced in male BALB/c mice by placing them on small platforms (d = 3.5 cm) surrounded by water for 24 or 72 h. This experimental model contains several factors of stress, like rapid eye movement (REM) sleep deprivation, isolation, immobilization and falling into the water. After 24 h small platform stress exposure latency to sleep was measured after the administration of the benzodiazepine receptor agonist diazepam (1.0 and 2.5 mg/kg, Lp.) and the benzodiazepine receptor inverse agonist R o 15-4513 (1.0 mg/kg, i.p.). As could be expected. diazepam significantly shortened the latency to sleep. Surprisingly the administration of Ro 15-45 I3 also shortened the latency to sleep. In addition [3H]Ro 15-4513 binding was measured in the cerebellum of control and small platform stressed mice. Small platform stress for 24 h did not alter the maximal number of ['HIRo 15-4513 binding sites (Bmax) and decreased their affinity (K,,). Sinall platform stress for 72 h significantly increased the number of ['HIRo 15-4513 binding sites and decreased their affinity. These cffects were due to changes in diazepam-sensitive binding. In conclusion, it could be supposed that exposure of mice to small platform stress causes changes in the function of the ['HIRo 15-4513 binding sites, probably a shift of binding sites toward agonist conformation, that leads to changes in the effects of Ro 15-4513. 0 2000 Editions scientifiques et medicales Elsevier SAS stress / HEM sleep deprivation / sleep / 13HIRo 15-4513 binding
Male Wistar rats were treated with: 1st saline (controls); 2nd saline and Diaz 2.5 mg/kg; 3rd Tac... more Male Wistar rats were treated with: 1st saline (controls); 2nd saline and Diaz 2.5 mg/kg; 3rd Tac 1 mg/kg and Diaz; 4th Don 0.5 mg/kg and Diaz; 5th Riv 1 mg/kg and Diaz. Learning sessions in active avoidance test were given on 5 days and on 12th day memory retention was measured. The parameters observed: avoidances, escapes and intertial crossings. In stepthrough passive avoidance learning session was given on 2 days, short memory retention session -on 3rd day, and long memory retention measurement on 10th day. The latency of reaction was 3 minutes.
The aim of this work was to study the effects of the nitric oxide synthase inhibitor N G -nitro-L... more The aim of this work was to study the effects of the nitric oxide synthase inhibitor N G -nitro-L-arginine (L-NOARG) on the sedative and toxic effects of ethanol in rats. Ethanol at a dose of 3 g/kg, intraperitoneally induced sleep in rats (sleep time: 111.2∫10.3 min.). Administration of the nitric oxide synthase inhibitor L-NOARG (20 and 40 mg/ kg, intraperitoneally) 30 min. before ethanol significantly increased the duration of ethanol-induced sleep. L-NOARG at doses of 20 and 40 mg/kg reduced the exploratory activity of rats in the open-field test and significantly enhanced the sedative effect of ethanol in this test. It is possible that this effect is not caused by the interaction of ethanol with nitric oxide pathways but by synergistic CNS depression caused by ethanol and L-NOARG. L-NOARG (20 and 40 mg/kg) had no effect on ethanol concentrations in blood after acute ethanol administration (2 and 3 g/kg). Moreover, the combined administration of ethanol (2 g/kg) and L-NOARG (20 and 40 mg/kg) caused a decrease in the body weight of animals, observed for 14 days. Also, livers of these rats were studied for necrosis and connective tissue reaction. In histological studies L-NOARG at a dose of 40 mg/kg had no effect on hepatic necrosis caused by the acute administration of ethanol but strenghtened connective tissue reaction. L-NOARG is widely used in pharmacological studies, including those concerning the effects of ethanol. However, on the basis of our data the possibility of toxic interactions with ethanol should be considered.
The objective of the study was to investigate the effects of the nitric oxide synthase (NOS) inhi... more The objective of the study was to investigate the effects of the nitric oxide synthase (NOS) inhibitors 7-nitroindazole (7-NI), N(G)-nitro-L-arginine (L-NOARG), and N(G)-nitro-L-arginine methyl ester (L-NAME) on the behavior of mice in the staircase test. NOS inhibitors 7-NI (20-120 mg/kg), L-NOARG (20 and 40 mg/kg), and L-NAME (20 and 40 mg/kg) were administered intraperitoneally (i.p.) 30 min prior to the staircase test. Staircase test consisted of placing a mouse in an enclosed staircase with five steps and recording the number of rearings made and the number of steps climbed during a 3-min period. 7-NI and L-NOARG did not have a significant effect on the behavior of mice in the staircase test. L-NAME caused a decrease in the number of rearings without changes in the number of steps taken. NOS inhibitor L-NAME but not 7-NI or L-NAME induced an anxiolytic effect in the staircase test.
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2001
Pokk Paavo and Marika V~ili: Small platform stress increases exploratory activity of mice in stai... more Pokk Paavo and Marika V~ili: Small platform stress increases exploratory activity of mice in staircase test.
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2004
The aim of the work was to study the effects of litter and the nitric oxide synthase (NOS) inhibi... more The aim of the work was to study the effects of litter and the nitric oxide synthase (NOS) inhibitor N G -nitro-l-arginine (l-NOARG) on the behaviour of mice after acute and chronic ethanol administration and withdrawal. Male outbred NIH/S mice, from 21 litters, were distributed among experimental groups and subjected to acute and chronic ethanol administration. After acute or chronic ethanol administration, the effects of l-NOARG on the behaviour of mice in the plus-maze test were studied. Acute ethanol (1 g/kg, i.p.), l-NOARG (20 and 40 mg/kg, i.p.) and their combination induced an anxiolytic effect. Furthermore, the values for the representatives of different litters tended to be either above or below the group mean, irrespective of the drug treatment. Chronic ethanol administration (23 days by inhalation) induced an anxiolytic effect and ethanol withdrawal induced an anxiogenic effect in the plus-maze. The administration of l-NOARG (20 mg/ kg, i.p.) induced an anxiolytic effect in control mice and had no effect on ethanol-intoxicated mice, but attenuated the anxiogenic effect of ethanol withdrawal in the plus-maze. However, after chronic ethanol administration and withdrawal, litter had no effect on the behaviour of mice. If the litter is a significant determinant in the behaviour of outbred mice, then the use of information about the litter origin of animals could serve for the purposes of reduction. But only if this information is available from breeders. D
The hepatoprotective effects and pharmacokinetics of trans-resveratrol and hydroxystilbenes of th... more The hepatoprotective effects and pharmacokinetics of trans-resveratrol and hydroxystilbenes of the garden rhubarb (Rheum rhaponticum L., R. rhaponticum) root ethanol extract were studied.
The effect of baclofen on the locomotor activity of control and small-platform-stressed mice was ... more The effect of baclofen on the locomotor activity of control and small-platform-stressed mice was studied. In the small platform technique, mice are forced to stay on small platforms (d= 3.5 cm) surrounded by water for 24 h. Small platform stress increased the locomotor activity of mice in the actometer. Baclofen administered at doses of 0.25, 0.5 and 1.0 mg kg(-1)(i.p.) had no effect on the locomotor activity of control mice. In small-platform-stressed mice, the locomotor depressant effect of baclofen was pronounced, being statistically significant at a dose of 1.0 mg kg(-1). These data suggest that small platform stress induces hypersensitivity of mice to the motor depressant effect of baclofen. On the basis of these data it could be proposed that small platform stress induces changes in the function of GABA(B)receptors and that GABA(B)receptors participate in the behavioural changes caused by small platform stress.
The effects of flumazenil, Ro 15-4513 and &bgr;-CCM in the staircase test wer... more The effects of flumazenil, Ro 15-4513 and &bgr;-CCM in the staircase test were studied in control and small platform (SP) stressed mice. SP stress was induced by placing mice on small platforms (3.5 cm in diameter) surrounded by water for 24 h. This model contains several factors of stress, such as rapid eye movement sleep deprivation, isolation, immobilization and falling
Small platform stress was induced in male BALB/c mice by placing them on small platforms (d = 3.5... more Small platform stress was induced in male BALB/c mice by placing them on small platforms (d = 3.5 cm) surrounded by water for 24 or 72 h. This experimental model contains several factors of stress, like rapid eye movement (REM) sleep deprivation, isolation, immobilization and falling into the water. After 24 h small platform stress exposure latency to sleep was measured after the administration of the benzodiazepine receptor agonist diazepam (1.0 and 2.5 mg/kg, Lp.) and the benzodiazepine receptor inverse agonist R o 15-4513 (1.0 mg/kg, i.p.). As could be expected. diazepam significantly shortened the latency to sleep. Surprisingly the administration of Ro 15-45 I3 also shortened the latency to sleep. In addition [3H]Ro 15-4513 binding was measured in the cerebellum of control and small platform stressed mice. Small platform stress for 24 h did not alter the maximal number of ['HIRo 15-4513 binding sites (Bmax) and decreased their affinity (K,,). Sinall platform stress for 72 h significantly increased the number of ['HIRo 15-4513 binding sites and decreased their affinity. These cffects were due to changes in diazepam-sensitive binding. In conclusion, it could be supposed that exposure of mice to small platform stress causes changes in the function of the ['HIRo 15-4513 binding sites, probably a shift of binding sites toward agonist conformation, that leads to changes in the effects of Ro 15-4513. 0 2000 Editions scientifiques et medicales Elsevier SAS stress / HEM sleep deprivation / sleep / 13HIRo 15-4513 binding
Male Wistar rats were treated with: 1st saline (controls); 2nd saline and Diaz 2.5 mg/kg; 3rd Tac... more Male Wistar rats were treated with: 1st saline (controls); 2nd saline and Diaz 2.5 mg/kg; 3rd Tac 1 mg/kg and Diaz; 4th Don 0.5 mg/kg and Diaz; 5th Riv 1 mg/kg and Diaz. Learning sessions in active avoidance test were given on 5 days and on 12th day memory retention was measured. The parameters observed: avoidances, escapes and intertial crossings. In stepthrough passive avoidance learning session was given on 2 days, short memory retention session -on 3rd day, and long memory retention measurement on 10th day. The latency of reaction was 3 minutes.
The aim of this work was to study the effects of the nitric oxide synthase inhibitor N G -nitro-L... more The aim of this work was to study the effects of the nitric oxide synthase inhibitor N G -nitro-L-arginine (L-NOARG) on the sedative and toxic effects of ethanol in rats. Ethanol at a dose of 3 g/kg, intraperitoneally induced sleep in rats (sleep time: 111.2∫10.3 min.). Administration of the nitric oxide synthase inhibitor L-NOARG (20 and 40 mg/ kg, intraperitoneally) 30 min. before ethanol significantly increased the duration of ethanol-induced sleep. L-NOARG at doses of 20 and 40 mg/kg reduced the exploratory activity of rats in the open-field test and significantly enhanced the sedative effect of ethanol in this test. It is possible that this effect is not caused by the interaction of ethanol with nitric oxide pathways but by synergistic CNS depression caused by ethanol and L-NOARG. L-NOARG (20 and 40 mg/kg) had no effect on ethanol concentrations in blood after acute ethanol administration (2 and 3 g/kg). Moreover, the combined administration of ethanol (2 g/kg) and L-NOARG (20 and 40 mg/kg) caused a decrease in the body weight of animals, observed for 14 days. Also, livers of these rats were studied for necrosis and connective tissue reaction. In histological studies L-NOARG at a dose of 40 mg/kg had no effect on hepatic necrosis caused by the acute administration of ethanol but strenghtened connective tissue reaction. L-NOARG is widely used in pharmacological studies, including those concerning the effects of ethanol. However, on the basis of our data the possibility of toxic interactions with ethanol should be considered.
The objective of the study was to investigate the effects of the nitric oxide synthase (NOS) inhi... more The objective of the study was to investigate the effects of the nitric oxide synthase (NOS) inhibitors 7-nitroindazole (7-NI), N(G)-nitro-L-arginine (L-NOARG), and N(G)-nitro-L-arginine methyl ester (L-NAME) on the behavior of mice in the staircase test. NOS inhibitors 7-NI (20-120 mg/kg), L-NOARG (20 and 40 mg/kg), and L-NAME (20 and 40 mg/kg) were administered intraperitoneally (i.p.) 30 min prior to the staircase test. Staircase test consisted of placing a mouse in an enclosed staircase with five steps and recording the number of rearings made and the number of steps climbed during a 3-min period. 7-NI and L-NOARG did not have a significant effect on the behavior of mice in the staircase test. L-NAME caused a decrease in the number of rearings without changes in the number of steps taken. NOS inhibitor L-NAME but not 7-NI or L-NAME induced an anxiolytic effect in the staircase test.
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