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M Väli

Publications and source records attributed to M Väli.

9 recordsLinked to original sources

Small platform stress increases exploratory activity of mice in staircase test.

Small platform (SP) stress was induced by placing mice on small platforms (3.5 cm diameter) surrounded by water for 24 h. This model contains several factors of stress like rapid eye movement (REM) sleep deprivation, isolation, immobilization and falling into the water. The staircase test consisted of placing a mouse in an enclosed staircase with 5 steps and recording (1) the number of steps and (2) rearings made during 3 min. SP stress increased the exploratory activity of mice in the staircase test as evidenced by an increase in the number of steps and rearings made In control mice diazepam (0.25 and 0.5 mg/kg) induced an anxiolytic effect in the staircase test as evidenced by a decrease in the number of rearings without changes in the number of steps. In SP stressed mice the anxiolytic effect of diazepam was not seen and the sedative effect as evidenced by a decrease in the number of steps was more pronounced. Buspirone at a dose of 1.0 mg/kg did not have effect on the behaviour of control or SP stressed mice in the staircase test. To study possible diurnal variations the staircase test was carried out at 3 different times of a day (08:00, 14:00, 20:00) with control and SP stressed mice. The exploratory activity of control mice in the staircase test gradually increased from 08:00 to 20:00 as evidenced by an increased number of steps and rearings made. SP stress increased the exploratory activity of mice irrespective of the time of testing. In conclusion, on the basis of these data the authors can propose that SP stress increases the exploratory activity of mice in the staircase test and induces a hyposensitivity of mice to the anxiolytic effect of diazepam. The effect of SP stress on the behaviour of mice in the staircase test is not caused by the disruptance of diurnal rhythms.

Animals↗

The effects of flumazenil, Ro 154513 and beta-CCM on the behaviour of control and stressed mice in the staircase test.

The effects of flumazenil, Ro 154513 and beta-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 into the water. The staircase test consisted of placing a mouse in an enclosed staircase with five steps and recording: (i) the number of rearings and (ii) steps made during 3 min. SP stress increased the exploratory activity of mice in the staircase test as demonstrated by an increase in the number of rearings and steps made. In control mice flumazenil (2.0 and 10.0 mg/kg), Ro 15-4513 (1.0 and 3.0 mg/kg) and beta-CCM (1.0 and 2.0 mg/kg) exerted an anxiogenic effect that was demonstrated by an increase in the number of rearings without significant changes in the number of steps. Similar to control mice, flumazenil induced an anxiogenic effect in SP stressed mice as demonstrated by an increase in the number of rearings. However, the sedative effect of flumazenil as demonstrated by a decrease in the number of steps made was more pronounced in SP stressed mice. In the SP stressed mice, the anxiogenic effect of Ro 15-4513 and beta-CCM was masked by their strong sedative effect and a decrease in both measures of exploratory activity (number of rearings and number of steps). These data suggest that SP stress induces hypersensitivity to the sedative effect of flumazenil, Ro 15-4513 and beta-CCM in the staircase test.

Animals↗

The effect of baclofen on the locomotor activity of control and small-platform-stressed mice.

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.

Animals↗

The influence of the nitric oxide synthase inhibitor L-NOARG on the effects of ethanol in rats after acute ethanol administration.

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 strengthened 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.

Animals↗

An age-related difference in the ratio of sudden coronary death over acute myocardial infarction in Estonian males.

The present study was undertaken to investigate the in-hospital and the out-of-hospital mortality rate from ischemic heart disease (IHD). The age-related incidence of acute myocardial infarction (AMI) and the number of sudden coronary deaths (SCD) in males in South Estonia with the population of approximately 400,000 inhabitants were subjected to comparative analysis covering a period of 17 years (1980-1996). The annual AMI incidence rate per 100,000 males was 30.8 (95% CI, 27.2-34.4) in the younger age group (20-39) and 393.1 (382-404) in the older age group (40-84); the rates for SCD were 19.2 (16.4-22) and 120 (114-126), respectively. The ratio of annual incidence rate of SCD/AMI in the younger group was significantly higher than that in the older group (chi2 = 5.23; P < 0.05). Thus, the out-of-hospital SCD seems to be of even more relative importance in the total mortality from IHD in young males than it is in older males.

Adult↗

No deterioration of glucose tolerance in weight cycling obese.

OBJECTIVE: To evaluate whether weight cycling is detrimental to the changes in glucose tolerance in obese individuals without overt NIDDM and related to the amplitude of weight cycling. DESIGN: Historical prospective observational study of a hospital-based cohort. SUBJECTS: One hundred twenty-five obese individuals drawn from the medical records of the Hospital of Endocrinology, University of Tartu, in whom at least one weight cycle was detected. Selected cutoff value for weight cycling set to 3, 6, 9 and 12 kg of weight loss and subsequent regain. MEASUREMENTS: Weight measurements and oral glucose tolerance tests. The latest oral glucose tolerance test and the one during the first visit compared by the 2 h blood glucose values and areas under the blood glucose curve. RESULTS: No deterioration of glucose tolerance recorded in any of the groups with different cutoff values for weight cycling. No trend towards the deterioration of glucose tolerance with increasing amplitude of weight cycles. CONCLUSION: We cannot claim that weight cycling is detrimental to glucose tolerance in non-diabetic obese individuals. This effect is independent of the amplitude of weight cycling. Weight reduction may be recommended to obese individuals for the prevention of NIDDM even if it is unsuccessful and the phenomenon of weight cycling results.

Adult↗

The effects of the nitric oxide synthase inhibitor 7-nitroindazole on ethanol pharmacokinetics in rats after acute and chronic ethanol administration.

The aim of this work was to study the effects of the nitric oxide synthase (NOS) inhibitors 7-nitroindazole (7-NI) and NG-nitro-L-arginine (L-NOARG) on the effects and pharmacokinetics of ethanol in rats. Ethanol at a dose of 4 g/kg, i.p. induced sleep in rats (sleep time: 117.2+/-30.7 min). Administration of the NOS inhibitors 7-NI (20 mg/kg, i.p.) and L-NOARG (20 mg/kg, i.p.) 30 min before ethanol significantly increased the duration of ethanol-induced sleep. L-NOARG also significantly increased the toxicity of ethanol as evidenced by increased post-experimental lethality. Ethanol at a dose of 2 g/kg (i.p.) did not induce sleep in vehicle-treated rats; however, the combined administration of ethanol (2 g/kg) and 7-NI at doses of 40, 80, and 120 mg/kg caused sleep, for 49.4+/-3.7, 204.0+/-13.3, and 447.5+/-62.8 min, respectively. L-NOARG (20 mg/kg) had no effect on ethanol concentrations in blood after acute ethanol administration (4 g/kg). 7-NI in lower doses (20 and 40 mg/kg) had no effect and in higher doses (80 and 120 mg/kg) significantly slowed ethanol clearance during the 12 h after ethanol administration. The effect of 7-NI (20 mg/kg) on ethanol pharmacokinetics after chronic ethanol administration (inhalation for 18 days) was also studied. The administration of 7-NI immediately after the end of ethanol exposure had a pronounced effect on ethanol pharmacokinetics; in 7-NI-treated rats the fall in ethanol concentrations was significantly slower as compared with vehicle-treated rats. In 7-NI-treated rats, blood-ethanol levels were higher at 3, 6, 9, and 12 h after the end of ethanol exposure.

Animals↗

The effects of the nitric oxide synthase inhibitor 7-nitroindazole on the behaviour of mice after chronic ethanol administration.

The effects of the nitric oxide synthase (NOS) inhibitor 7-nitroindazole (7-NI) on the behaviour of mice after chronic and acute ethanol administration were studied. Male albino mice received ethanol by inhalation for 25 days. The plus-maze and staircase tests were carried out with control, ethanol-intoxicated and ethanol-withdrawn mice (7.5 h after the end of ethanol administration). The administration of NOS inhibitor 7-NI [20.0 mg/kg, intraperitoneally (i.p.)] 60 min or 7.5 h before the plus-maze test induced an anxiolytic effect in control mice. Chronic ethanol administration induced an anxiolytic, and ethanol withdrawal an anxiogenic, effect in mice. The administration of 7-NI (20.0 mg/kg, i.p.) caused behavioural depression in ethanol-intoxicated mice, but had no effect on the behaviour of ethanol-withdrawn mice. 7-NI had no effect on the behaviour of control mice in the staircase test. Chronic ethanol administration increased, and ethanol withdrawal decreased, the locomotor activity of mice in the staircase test. Likewise, in the plus-maze test, administration of 7-NI caused behavioural depression in ethanol-intoxicated mice, but had no effect on the behaviour of ethanol-withdrawn mice. In additional experiments, vehicle or 7-NI (20.0-120.0 mg/kg, i.p.) were administered 30 min before ethanol (3.0 g/kg, i.p.). 7-NI dose-dependently increased the duration of ethanol-induced sleep and inhibited ethanol clearance. On the basis of these data we can propose that the NO system has no major role in behavioural changes caused by ethanol withdrawal. At the same time NOS inhibitors can cause synergistic CNS depression with ethanol.

Animals↗

Small platform stress increases.

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, i.p.) and the benzodiazepine receptor inverse agonist Ro 15-4513 (1.0 mg/kg, i.p.). As could be expected, diazepam significantly shortened the latency to sleep. Surprisingly the administration of Ro 15-4513 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 [3H]Ro 15-4513 binding sites (Bmax) and decreased their affinity (K(D)). Small platform stress for 72 h significantly increased the number of [3H]Ro 15-4513 binding sites and decreased their affinity. These effects 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 [3H]Ro 15-4513 binding sites, probably a shift of binding sites toward agonist conformation, that leads to changes in the effects of Ro 15-4513.

Affinity Labels↗