Scandinavian Journal of Laboratory Animal Science, 2007
Environmental enrichment (EE) has been associated with many effects on the behavior of laboratory... more Environmental enrichment (EE) has been associated with many effects on the behavior of laboratory animals. The term EE is rather vague, often referring to a variety of item combinations as if what is added to the cage has no significance. EE is indeed housing refinement, and therefore more exact terms should be used to clarify the situation. This study was designed to assess whether access to a nest box (NB) could modify behavior of BALB/c mice in the plus-maze test. Two series of experiments were done with an aspen NB (11 x 11 x 7 cm, wall thickness 1.5 cm, two round holes (d = 3 cm) at opposite sides. Control mice had no added item in the cage. The plus-maze consisted of two open (8 x 17 cm) and two closed arms (8 x 17 x 30 cm) connected by a central platform (8 x 8 cm). Mice were placed on the central platform facing an open arm. During five minutes, the numbers of entries made onto the open and into the closed arms were recorded. From this data, the percentages...
Scandinavian Journal of Laboratory Animal Science, 2008
The objective of this study was to investigate the effects of litter and weight on the behavior o... more The objective of this study was to investigate the effects of litter and weight on the behavior of mice. Male outbred NIH/S mice from 8 litters were randomly distributed among 6 cages and subjected to the plus-maze and staircase tests. The litter from which the animals had originated had a significant effect on the behavior of mice in the plus-maze test; furthermore addition of the covariates final weight and weight gain had no effect on significance or explanatory value. It is proposed that litter origin might influence the adaptation processes, the development of social status and consequently, the behavior of mice. Differences attributable to litter were not observed in the staircase test, but when both weight parameters were added as covariates this proved to be significant. Though the source of these litter-related differences remains to be clarified, these differences do have a significant effect on the behavior of mice. Therefore they need to be considered s...
International Journal of Environmental Research and Public Health
Large oil shale resources are found in Eastern Estonia, where the mineral resource is mined, exca... more Large oil shale resources are found in Eastern Estonia, where the mineral resource is mined, excavated, and used for electricity generation and shale oil extraction. During industrial activities in the last 100 years, pollutants have been emitted in large amounts, some of which are toxic and carcinogenic. The current study aims to analyse time trends in cancer incidence in the oil shale industry-affected areas and compare them with overall cancer incidence rates and trends in Estonia. We analysed Estonian Cancer Registry data on selected cancer sites that have been previously indicated to have relationships with industrial activities like oil shale extraction. We included lung cancer, kidney cancer, urinary bladder cancer, leukaemia, breast cancer, and non-Hodgkin’s lymphoma. A statistically significantly higher lung cancer age-standardized incidence rate (ASIR) was found during the study period (1992—2015) only in males in the oil shale areas as compared to males in Estonia overall...
Second-generation antipsychotics are commonly used to treat schizophrenia, but may cause metaboli... more Second-generation antipsychotics are commonly used to treat schizophrenia, but may cause metabolic syndrome (MetS) in a subset of patients. The mechanisms of antipsychotic-related metabolic changes remain to be established, especially in first-episode psychosis (FEP) patients. In the present study, we used a chip technology to measure metabolic (C-peptide, insulin, leptin, adiponectin and resistin) and inflammatory biomarkers (ferritin, interleukin-6, interleukin-1α, tumour necrosis factor-α and plasminogen activator inhibitor-1) in the serum samples of a population of FEP patients before and after 7 months of antipsychotic drug treatment, compared to control subjects (CS). The comparison of these markers in antipsychotic-naïve FEP patients (N = 38) and CS (N = 37) revealed significantly higher levels of ferritin (P = .004), and resistin (P = .03) and lower level of leptin (P = .03) among FEP patients group. Seven months of antipsychotic drug treatment in patients (N = 36) ameliorated clinical symptoms, but increased significantly body mass index (BMI; P = .002) and these changes were accompanied by increased levels of C-peptide (P = .03) and leptin (P = .02), as well as decreased level of adiponectin (P = .01). Seven months of antipsychotic drug treatment suppressed the clinical symptoms of psychosis whereas caused imbalance in metabolic biomarkers and increased BMI. These findings provide insight into antipsychotic-induced MetS and refer to problems in insulin processing already present in the early stage of the chronic psychotic disorder.
The experiments on male albino rats have shown that 15 days haloperidol (0.5 mg/kg) and racloprid... more The experiments on male albino rats have shown that 15 days haloperidol (0.5 mg/kg) and raclopride (1 mg/kg) treatment, but not acute administration, causes the increase of density of sigma receptors in the brain. The number of phencyclidine receptors was also elevated, but this increase was not statistically evident. The behavioral effects of ketamine (5 mg/kg) were evidently decreased after long-term haloperidol and raclopride treatment. The motor stimulation and stereotyped behavior induced by apomorphine (0.15 mg/kg) were increased only after treatment of haloperidol, but not raclopride. It seems probable that repeated neuroleptic (haloperidol and raclopride) treatment causes the hyposensitivity of sigma and phencyclidine receptors, despite the increase of their number. It is possible that this change is related to the depolarization inactivation of dopamine neurons caused by repeated neuroleptic administration.
Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova
In experiments on male mice and rats, long-term haloperidol administration (0.25 mg/kg twice a da... more In experiments on male mice and rats, long-term haloperidol administration (0.25 mg/kg twice a day during 15 days) significantly changed behavioural effects of caerulein, an agonist of CCK-8 receptors. As a rule, the effects of caerulein were reduced or inverted; only long-term antagonism with amphetamine motor excitation in rats increased after the cessation of haloperidol administration. The decrease or inversion of caerulein's effects was connected with reduction of high-affinity dopamine2- and low-affinity CCK-8 receptors' density, reflecting the inhibition of some interneurons' activity in subcortical forebrain structures after haloperidol treatment. A more pronounced inhibition of dopamine's release by caerulein was the reason for the increased antiamphetamine action after long-term haloperidol treatment. It seems possible that both above mechanisms are involved in the antipsychotic action of haloperidol.
The stimulatory effect of morphine, dexmedetomidine (an alpha 2-adrenoceptor agonist), 1-(3-chlor... more The stimulatory effect of morphine, dexmedetomidine (an alpha 2-adrenoceptor agonist), 1-(3-chlorophenyl)-piperazine (m-CPP, a 5-HT1B agonist), U-50488H (a kappa-opioid receptor agonist), pimozide (a dopamine antagonist), and restraint stress on prolactin and growth hormone (GH) secretion was compared during cold exposure (4 degrees C) and under basal conditions (30 degrees C) in male rats. Rectal temperature was also measured. The stimulatory effect of morphine, dexmedetomidine, m-CPP, and partially U-50488H on prolactin secretion was attenuated in rats kept at 4 degrees C. Cold exposure did not abolish prolactin release induced by pimozide and restraint stress. Cold exposure also antagonized the effect of morphine and dexmedetomidine on GH secretion. The stimulatory effect of morphine on prolactin and GH secretion was restored in the warm environment despite the sustained hypothermia. Cold exposure blocked the stimulatory effect of morphine on prolactin secretion in rats that were...
N-Methyl-D-aspartate (NMDA, 20 mg/kg) produced a clear decrease in mouse exploration in open part... more N-Methyl-D-aspartate (NMDA, 20 mg/kg) produced a clear decrease in mouse exploration in open parts of an elevated plus-maze. Paradoxically, 40 mg/kg NMDA did not modify the behavior of the mice in the plus-maze. NMDA at a dose of 80 mg/kg again depressed the exploratory activity of mice, but this effect was accompanied with tremor and compulsive tail biting. The 'anti-exploratory' dose of NMDA (20 mg/kg) increased, whereas the 'tremorigenic' dose (80 mg/kg) significantly decreased the number of cholecystokinin (CCK) binding sites in the mouse cerebral cortex. The competitive NMDA antagonist (+/-)-CPP (2.5-5 mg/kg) and the non-competitive antagonist MK-801 (0.25 mg/kg) antagonized the anti-exploratory effect of NMDA (20 mg/kg). The tricyclic antidepressant imipramine (5 mg/kg, but not 1 or 10 mg/kg) also attenuated the inhibition of exploratory activity induced by NMDA. Of three CCK receptor antagonists tested, the unselective CCK antagonist proglumide (1 mg/kg, but n...
Systemic treatment with cholecystokinin octapeptide (CCK-8, 2.5-10 micrograms/kg, s.c.), a non-se... more Systemic treatment with cholecystokinin octapeptide (CCK-8, 2.5-10 micrograms/kg, s.c.), a non-selective CCK agonist, decreased the exploratory activity of mice in an elevated plus-maze. At higher doses (5-10 micrograms/kg) CCK-8 reduced the frequency of rearing, but only 10 micrograms/kg of CCK-8 significantly inhibited the number of line crossings in the open-field test. A preferential CCKB antagonist L-365,260 (1 and 100 micrograms/kg, i.p.) and a non-selective CCK antagonist proglumide (0.1-1 microgram/kg, i.p.) potentiated the anti-exploratory effect of CCK-8 (2.5 micrograms/kg). Devazepide, a preferential CCKA antagonist, only at a high dose (100 micrograms/kg) tended to increase the action of CCK-8 in the plus-maze. However, the concomitant treatment of CCK-8 with L-365,260 and proglumide, differently from devazepide, also suppressed the locomotor activity in the open-field test. Therefore, it is likely that the potentiation by CCK antagonists of the anti-exploratory effect o...
Scandinavian Journal of Laboratory Animal Science, 2007
Environmental enrichment (EE) has been associated with many effects on the behavior of laboratory... more Environmental enrichment (EE) has been associated with many effects on the behavior of laboratory animals. The term EE is rather vague, often referring to a variety of item combinations as if what is added to the cage has no significance. EE is indeed housing refinement, and therefore more exact terms should be used to clarify the situation. This study was designed to assess whether access to a nest box (NB) could modify behavior of BALB/c mice in the plus-maze test. Two series of experiments were done with an aspen NB (11 x 11 x 7 cm, wall thickness 1.5 cm, two round holes (d = 3 cm) at opposite sides. Control mice had no added item in the cage. The plus-maze consisted of two open (8 x 17 cm) and two closed arms (8 x 17 x 30 cm) connected by a central platform (8 x 8 cm). Mice were placed on the central platform facing an open arm. During five minutes, the numbers of entries made onto the open and into the closed arms were recorded. From this data, the percentages...
Scandinavian Journal of Laboratory Animal Science, 2008
The objective of this study was to investigate the effects of litter and weight on the behavior o... more The objective of this study was to investigate the effects of litter and weight on the behavior of mice. Male outbred NIH/S mice from 8 litters were randomly distributed among 6 cages and subjected to the plus-maze and staircase tests. The litter from which the animals had originated had a significant effect on the behavior of mice in the plus-maze test; furthermore addition of the covariates final weight and weight gain had no effect on significance or explanatory value. It is proposed that litter origin might influence the adaptation processes, the development of social status and consequently, the behavior of mice. Differences attributable to litter were not observed in the staircase test, but when both weight parameters were added as covariates this proved to be significant. Though the source of these litter-related differences remains to be clarified, these differences do have a significant effect on the behavior of mice. Therefore they need to be considered s...
International Journal of Environmental Research and Public Health
Large oil shale resources are found in Eastern Estonia, where the mineral resource is mined, exca... more Large oil shale resources are found in Eastern Estonia, where the mineral resource is mined, excavated, and used for electricity generation and shale oil extraction. During industrial activities in the last 100 years, pollutants have been emitted in large amounts, some of which are toxic and carcinogenic. The current study aims to analyse time trends in cancer incidence in the oil shale industry-affected areas and compare them with overall cancer incidence rates and trends in Estonia. We analysed Estonian Cancer Registry data on selected cancer sites that have been previously indicated to have relationships with industrial activities like oil shale extraction. We included lung cancer, kidney cancer, urinary bladder cancer, leukaemia, breast cancer, and non-Hodgkin’s lymphoma. A statistically significantly higher lung cancer age-standardized incidence rate (ASIR) was found during the study period (1992—2015) only in males in the oil shale areas as compared to males in Estonia overall...
Second-generation antipsychotics are commonly used to treat schizophrenia, but may cause metaboli... more Second-generation antipsychotics are commonly used to treat schizophrenia, but may cause metabolic syndrome (MetS) in a subset of patients. The mechanisms of antipsychotic-related metabolic changes remain to be established, especially in first-episode psychosis (FEP) patients. In the present study, we used a chip technology to measure metabolic (C-peptide, insulin, leptin, adiponectin and resistin) and inflammatory biomarkers (ferritin, interleukin-6, interleukin-1α, tumour necrosis factor-α and plasminogen activator inhibitor-1) in the serum samples of a population of FEP patients before and after 7 months of antipsychotic drug treatment, compared to control subjects (CS). The comparison of these markers in antipsychotic-naïve FEP patients (N = 38) and CS (N = 37) revealed significantly higher levels of ferritin (P = .004), and resistin (P = .03) and lower level of leptin (P = .03) among FEP patients group. Seven months of antipsychotic drug treatment in patients (N = 36) ameliorated clinical symptoms, but increased significantly body mass index (BMI; P = .002) and these changes were accompanied by increased levels of C-peptide (P = .03) and leptin (P = .02), as well as decreased level of adiponectin (P = .01). Seven months of antipsychotic drug treatment suppressed the clinical symptoms of psychosis whereas caused imbalance in metabolic biomarkers and increased BMI. These findings provide insight into antipsychotic-induced MetS and refer to problems in insulin processing already present in the early stage of the chronic psychotic disorder.
The experiments on male albino rats have shown that 15 days haloperidol (0.5 mg/kg) and racloprid... more The experiments on male albino rats have shown that 15 days haloperidol (0.5 mg/kg) and raclopride (1 mg/kg) treatment, but not acute administration, causes the increase of density of sigma receptors in the brain. The number of phencyclidine receptors was also elevated, but this increase was not statistically evident. The behavioral effects of ketamine (5 mg/kg) were evidently decreased after long-term haloperidol and raclopride treatment. The motor stimulation and stereotyped behavior induced by apomorphine (0.15 mg/kg) were increased only after treatment of haloperidol, but not raclopride. It seems probable that repeated neuroleptic (haloperidol and raclopride) treatment causes the hyposensitivity of sigma and phencyclidine receptors, despite the increase of their number. It is possible that this change is related to the depolarization inactivation of dopamine neurons caused by repeated neuroleptic administration.
Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova
In experiments on male mice and rats, long-term haloperidol administration (0.25 mg/kg twice a da... more In experiments on male mice and rats, long-term haloperidol administration (0.25 mg/kg twice a day during 15 days) significantly changed behavioural effects of caerulein, an agonist of CCK-8 receptors. As a rule, the effects of caerulein were reduced or inverted; only long-term antagonism with amphetamine motor excitation in rats increased after the cessation of haloperidol administration. The decrease or inversion of caerulein's effects was connected with reduction of high-affinity dopamine2- and low-affinity CCK-8 receptors' density, reflecting the inhibition of some interneurons' activity in subcortical forebrain structures after haloperidol treatment. A more pronounced inhibition of dopamine's release by caerulein was the reason for the increased antiamphetamine action after long-term haloperidol treatment. It seems possible that both above mechanisms are involved in the antipsychotic action of haloperidol.
The stimulatory effect of morphine, dexmedetomidine (an alpha 2-adrenoceptor agonist), 1-(3-chlor... more The stimulatory effect of morphine, dexmedetomidine (an alpha 2-adrenoceptor agonist), 1-(3-chlorophenyl)-piperazine (m-CPP, a 5-HT1B agonist), U-50488H (a kappa-opioid receptor agonist), pimozide (a dopamine antagonist), and restraint stress on prolactin and growth hormone (GH) secretion was compared during cold exposure (4 degrees C) and under basal conditions (30 degrees C) in male rats. Rectal temperature was also measured. The stimulatory effect of morphine, dexmedetomidine, m-CPP, and partially U-50488H on prolactin secretion was attenuated in rats kept at 4 degrees C. Cold exposure did not abolish prolactin release induced by pimozide and restraint stress. Cold exposure also antagonized the effect of morphine and dexmedetomidine on GH secretion. The stimulatory effect of morphine on prolactin and GH secretion was restored in the warm environment despite the sustained hypothermia. Cold exposure blocked the stimulatory effect of morphine on prolactin secretion in rats that were...
N-Methyl-D-aspartate (NMDA, 20 mg/kg) produced a clear decrease in mouse exploration in open part... more N-Methyl-D-aspartate (NMDA, 20 mg/kg) produced a clear decrease in mouse exploration in open parts of an elevated plus-maze. Paradoxically, 40 mg/kg NMDA did not modify the behavior of the mice in the plus-maze. NMDA at a dose of 80 mg/kg again depressed the exploratory activity of mice, but this effect was accompanied with tremor and compulsive tail biting. The 'anti-exploratory' dose of NMDA (20 mg/kg) increased, whereas the 'tremorigenic' dose (80 mg/kg) significantly decreased the number of cholecystokinin (CCK) binding sites in the mouse cerebral cortex. The competitive NMDA antagonist (+/-)-CPP (2.5-5 mg/kg) and the non-competitive antagonist MK-801 (0.25 mg/kg) antagonized the anti-exploratory effect of NMDA (20 mg/kg). The tricyclic antidepressant imipramine (5 mg/kg, but not 1 or 10 mg/kg) also attenuated the inhibition of exploratory activity induced by NMDA. Of three CCK receptor antagonists tested, the unselective CCK antagonist proglumide (1 mg/kg, but n...
Systemic treatment with cholecystokinin octapeptide (CCK-8, 2.5-10 micrograms/kg, s.c.), a non-se... more Systemic treatment with cholecystokinin octapeptide (CCK-8, 2.5-10 micrograms/kg, s.c.), a non-selective CCK agonist, decreased the exploratory activity of mice in an elevated plus-maze. At higher doses (5-10 micrograms/kg) CCK-8 reduced the frequency of rearing, but only 10 micrograms/kg of CCK-8 significantly inhibited the number of line crossings in the open-field test. A preferential CCKB antagonist L-365,260 (1 and 100 micrograms/kg, i.p.) and a non-selective CCK antagonist proglumide (0.1-1 microgram/kg, i.p.) potentiated the anti-exploratory effect of CCK-8 (2.5 micrograms/kg). Devazepide, a preferential CCKA antagonist, only at a high dose (100 micrograms/kg) tended to increase the action of CCK-8 in the plus-maze. However, the concomitant treatment of CCK-8 with L-365,260 and proglumide, differently from devazepide, also suppressed the locomotor activity in the open-field test. Therefore, it is likely that the potentiation by CCK antagonists of the anti-exploratory effect o...
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