Effect of Silicon Dioxide Nanoparticles on Syrian Hamsters Infected by Opisthorchis felineus: 1H MRS Study of the Brain.

In recent years, silicon dioxide nanoparticles have been widely used in medicine and the pharmaceutical industry, however, their effect on the brain has hardly been studied. We assessed the effects of long-term consumption of 5-nm amorphous silicon dioxide nanoparticles (SiO2-NPs) by Syrian hamsters infected with the trematodes Opisthorchis felineus on the hippocampus and frontal cortex. Spectroscopic determination of brain neurometabolites, performed using a horizontal Magnetic Resonance Imaging system at 11.7 Tesla magnetic field, has shown that the ratio of the excitatory neurotransmitters (glutamate + glutamine + aspartate) to the inhibitory ones (GABA + glycine) was higher in the animals infected with O. felineus. However, pre-consumption of the SiO2-NPs solution prevented this imbalance. In addition, the protective effect of SiO2-NPs on the level of myo-inositol and glycine was found. It is concluded that the use of SiO2-NPs can neutralize the negative effects of infectious factors on the brain.

Effectiveness of Repeated Administration of Praziquantel with Disodium Glycyrrhizinate and Two Enantiomers of Praziquantel on Opisthorchis felineus (Rivolta, 1884).

BACKGROUND: Nowadays, it is still important to develop effective anti-opisthorchiasis agents. In this work, we tested a complex of praziquantel (PZQ) with a plant origin compound-disodium glycyrrhizinate-in the ratio 1:10 PZQ:Na2GA, containing 11-fold less of the active ingredient. Our aim was to study various ways to treat trematode Opisthorchis felineus with this complex in vitro. Additionally, an in vitro comparison of the anthelmintic action was made among racemic-PZQ, (R)-PZQ, and (S)-PZQ on juvenile and adult maritae of O. felineus. METHODS: Worms extracted from the hamsters were subjected to various regimens of administration of the complex: once a day for 3 days or three times within 1 day. Moreover, mature maritae and juvenile worms of O. felineus were subjected to the comparison the anthelmintic effectiveness of racemic-PZQ, (R)-PZQ, and (S)-PZQ. RESULTS: The O. felineus maritae that received PZQ:Na2GA (1:10) thrice within 1 day were most strongly affected by the drug. Their motility substantially decreased already on the second day after the last dose, and the percentage of live worms by the end of the experimental period was the lowest. These results indicate a cumulative anthelmintic effect of this substance under the regimen "three times within 1 day." For the first time, we report that among the three substances (racemic-PZQ and two enantiomers), (R)-PZQ has the highest anthelmintic activity, toward both juvenile and sexually mature maritae of O. felineus. CONCLUSION: These findings suggest that the development of a supramolecular complex of (R)-PZQ with disodium glycyrrhizinate and administration of this complex three times within 1 day are promising approaches.

Physicochemical Properties and Anti-Opisthorchosis Effect of Mechanochemically Synthesized Solid Compositions of Praziquantel with Glycyrrhizic Acid Disodium Salt.

The mechanochemical preparation of solid compositions of praziquantel with plant saponin (glycyrrhizic acid disodium salt) is described. The study of a number of physicochemical parameters showed that dissolving solid compositions in water is accompanied by the inclusion of praziquantel molecules into micelles, which are formed in the solution of the glycyrrhizic acid disodium salt. Using the opisthorchiasis model caused by Opisthorchis felineus, we found a 4- to 11-fold increase in the anthelmintic activity of praziquantel in the composition as compared to the official praziquantel. According to the pharmacokinetic data, the use of the composition increased the bioavailability of praziquantel 3 times.

[Resistance of DBA/2J Mice to the Chronic Social Defeat Stress].

We investigated behavioral changes in male mice DBA/2J after the acquisition of a long experience of social defeats in agonistic interactions with aggressive partners of C57BL/6J and DBA/2J lines. The long experience of social defeat in DBA/2J mice did not change the strategy of theirbehavi6r during agonistic interactions. Reduced communicativeness and increased level of anxiety were found in the "partition" and "elevated plus maze" tests. There were no changes in locomotor activity in the "open field" test. After 20-30 days of social defeat stress there were no signs of depression, determined by the behavior during confrontations and in the Porsolt test. There was no sign of catalepsy, decreased exploratory be- havior and impaired social recognition. Thus, the mice of this strain can be considered relatively resis- tant to the development of depressive-like state under chronic social stress and may be used for the study of the mechanisms of such stability.

Effect of 2-aminoadamantane derivatives on behavior of mice in a modified light/dark test.

The effects of two derivatives of 2-aminoadamantane, enantiomers J447H and J579, on the behavior of male and female C57Bl/6J mice were studied using a modified light/dark test. The substances differed by their effects on the behavior of male mice. J579 reduced the number of rearings. J447H in a dose of 1 mg/kg affected more parameters: it reduced exploratory activity 1 h after administration and stimulated exploratory and motor activity in 2 h. In female mice, J447H significantly reduced the number of peepings into holes in 2 h after administration. The results indicate that further analysis of the effects of J579 and especially J447H is required.

Complex investigation of the effects of lambertianic acid amide in female mice under conditions of social discomfort.

The effects of chronic administration of a new substance lambertianic acid amide and previously synthesized methyl ester of this acid were compared in female mice living under conditions of social discomfort. For modeling social discomfort, female mouse was housed for 30 days in a cage with aggressive male mouse kept behind a transparent perforated partition and observed its confrontations with another male mouse daily placed to the cage. The new agent more effectively than lambertianic acid methyl ester improved communicativeness and motor activity of animals, reduced hypertrophy of the adrenal glands, and enhanced catalase activity in the blood. These changes suggest that lambertianic acid amide produces a pronounced stress-protective effect under conditions of social discomfort.

[Effects of buspirone complex with glycyrrhizic acid on behavior of mice with anxious-depressive state].

We report here studies of the effects of subchronic administration of 5-HT1A receptor agonist buspirone and its novel complex with glycyrrhizic acid (GA) to C57BL/6J mice at the different stages of the anxious-depressive state formation, induced by conditions of social stress. The experiment of agents' administration during the conditions of stress (beginning with initial stage) showed that only complex had a protective effect revealed in prevention of the anxiety with the high level of mice communicativeness maintenance. At the stage when the anxious-depressive state is completely formed, buspirone and its complex with GA decreased mice motor activity however complex--less significantly. Here we discuss a possible mechanism of action of investigated agents on the background of changes in the sensitivity of 5-HT1A receptors, induced by the formation of the anxious-depressive state of mice with experience of social stress. Despite of different effects of agents depending on the stage of the anxious-depressive state development, novel buspirone complex with GA has some advantage over buspirone.

[Development of movement disorders in DBA/2J male mice under repeated experience of aggression].

Changes in the behavior of DBA/2J mice after gaining repeated experience of aggression have been investigated. It was shown that the long-term experience of aggression led to development of hyperactivity estimated as increased motor activity in different tests: open field, elevated plus maze and during testing of reaction to a novelty. Symptoms of attention deficit estimated in the "partition" test as a reduction of the communicativeness and the lack of reaction to unfamiliar partner were noticed. Appearance of a large number of hyperkinesis manifested most often in the form of sudden involuntary head movements (jerks) was observed in the behavior of aggressive males during agonistic interactions. Most of the changes in the behavior of DBA/2J mice differed significantly from previously detected in the behavior of aggressive mice of C57BL/6J and CBA/Lac strains, suggesting a significant contribution of heredity that determines the features of behavioral disorders that occur under the influence of long-term experience of aggression. Similarity of symptomatics of movement disturbances in mice and in humans with some neurological diseases is discussed.

[Effects of buspirone on the behavior of female mice in a model of social discomfort].

The influence of acute and chronic (14 days) buspirone administration (1 mg/kg, intraperitoneally) on the behavior of C57BL/6J female mice, being in social discomfort, were studied. The conditions of social discomfort include the permanent habitation of females in the cage with aggressive males through a perforated partition and daily presence during intermale confrontations. The dynamic changes of 5-HT1A-receptor sensitivity in the brain of female mice, estimated by the female behavior after 30 min ofbuspirone administration, were discovered. The sensitivity increased at the early stages of pathological behavior development (10 days) and decreased after 20-30 days. Females who had reduced of 5-HT1A receptor sensitivity after 30 day of maintenance in social discomfort conditions also showed a decreased sensitivity on chronic buspirone administration.

[Effects of chronic buspirone treatment on female mice exposed to the long-lasting psychoemotional influence].

The effects of chronic treatment (30 days) with the 5-HT1A receptor partial agonist buspirone (0.05, 1 and 10 mg/kg i.p.) on the behaviour of C57BL/6J female mice exposed to long-lasting psychoemotional influence were studied. The influence involved forced living of each female with an aggressive male separated with a perforated transparent partition in the same cage and daily female's presence during 10-min intermale confrontations behind a partition caused by introducing of another male to the aggressive male. Chronic buspirone injection (in all used doses) did not affect the behaviour of females estimated in the "partitions" and "open field" tests at the end of the drug treatment. The anxiolytic effect of buspirone only at the dose of 1 mg/kg on the female's plus-maze behaviour was revealed. In the Porsolt, test buspirone in the dose of 1 mg/kg caused a slight increase in the duration of immobility indicating a slight pro-depressive effect. Thus, chronic buspirone treatment of females exposed to the long-lasting psychoemotional impact has a different effect on their behaviour depending on the dose and test conditions.

Effect of acute and chronic buspirone administration on communicativeness of mice with experience of defeats in social conflicts.

We studied the effect of 5-HT(1A)receptor agonist buspirone on behavior of male C57Bl/6J mice in the "partition" test, which reflects communicativeness of animals. Single administration of buspirone (1 mg/kg) to intact mice and animals experienced defeats in 20 intermale confrontations impaired their communicativeness, especially in intact animals. On the contrary, administration of buspirone (1 mg/kg) to losers starting from day 5 of intermale confrontations for 2 weeks produced a positive effect and prevented impairment of communicativeness by day 20 of confrontations. The role of brain 5-HT(1A)receptors in these processes is discussed.

Gender-related characteristics of responding to prolonged psychoemotional stress in mice.

The behavior of male and female C57BL/6J mice was studied after prolonged psychoemotional stress imposed by enforced cohabitation with an aggressive male on the other side of a partition in the cage and daily witnessing of 10-minute confrontations between the aggressor and another male placed with it. The elevated plus maze test demonstrated marked anxiety in mice of both genders after one month of psychoemotional stress. However, only females, but not males, showed an increase in the duration of passive swimming in the Porsolt test, along with some reduction in communicativeness in the partition test. Thus, these studies showed a more marked reaction to prolonged pscyhoemotional stress in females than in males.

[3H]SCH 23390 binding in various brain regions of C57BL/6J mice with repeated experience of victory or social defeat in agonistic interactions.

The binding of [3H]SCH 23390 has been studied in various brain regions of male mice with the experience of repeated victory (winners) or defeat (losers) gained over 10 (T10) and 20 (T20) days of daily agonistic confrontations. In the frontal cortex, B(max) of [3H]SCH 23390 binding sites was found to be increased in T10 losers and decreased in T20 losers when compared to the control mice. In the striatum, T10 and T20 winners had reduced values of [3H]SCH 23390 binding sites than the ones in the control mice. The K(d) was increased in the frontal cortex of T10 losers and T10 winners as well as in the amygdala of T20 losers. Reduced K(d) values were found in the striatum of all experimental groups as well as in the amygdala of T20 winners. Thus, both specific changes relating to social behavior patterns and non-specific ones in [3H]SCH 23390 binding were found in the brain regions of mice after 10 and 20 days of intermale confrontations.

[Mouse gender-related behavioral responses to long-lasting psychoemotional influence].

Behavior of male and female inbred mice of C57BL/6J strain was studied after long-lasting psychoemotional influence consisting of forced living with aggressive male separated with a perforated transparent partition in the same cage, and daily presence of males and female during 10-min intermale confrontations behind a partition caused by introducing intact mouse to an aggressive male. In a month, the increased level of anxiety in mice of both genders was revealed in the elevated plus-maze test. However, only females showed a longer time of passive swimming in the Porsolt's test. Under these conditions, females demonstrated some decrease of communication in the partition test. Accordingly, a more expressed behavior response was revealed in females in comparison with males on long-lasting psychoemotional influence.

[Effects of ethanol on metastasis of Lewis lung carcinoma in male mice with different social states].

The aim of this work was to study the effect of ethanol on experimental metastasis of Lewis lung carcinoma in male mice in positive or negative emotional states. Sensory contact model was used for generating animals with repeated experience of social victories or defeats. Tumor cells were injected into the tail vein after 20 days of agonistic interactions, and the number of metastases in the lung was calculated 16 days later. Group-housed mice were used as the controls. Mice of all experimental groups were chronically treated with ethanol (20%, 2 ml/kg of weight, i.p.) and saline during 7 days starting with the day of tumor cells injections. The experimental metastasis was shown to develop differently in mice with opposing social experience: saline-treated winners had significantly less metastases in the lung than the saline-treated losers. Chronic ethanol injections decreased the number of metastases in the losers, increased it in the winners and did not affect the controls. The results obtained indicate that effects if ethanol on Lewis lung carcinoma metastasis depend on psychoemotional status in male mice.

Behavioral effect of terahertz waves in male mice.

We studied the effect of terahertz waves (3.6 THz, 81.5 micro, 15 mW) on the behavior of mice. The mice perceived terahertz waves even after short-term exposure (15 min). The effect of terahertz waves was maximum in direct contact of the mice with the laser. Increased anxiety of experimental animals was observed on the next day after 30-min irradiation.

[Influence of experimental context on the development of anhedonia in male mice exposed to chronic social stress].

Consumption of 1% sucrose solution supplemented with 0.2% vanillin was studied in two experimental contexts in male mice living under chronic social stress induced by daily experience of defeats in agonistic interactions and leading to development of depression. In the first experiment, vanillin sucrose solution was made available as an option along with water during 10 days for mice living in group home cages. Then the mice were subjected to repeated social defeat stress and during exposure to stress they were provided with both vanillin sucrose solution and water using a free two-bottle choice paradigm. In the other experiment, vanillin sucrose solution was first offered to mice after 8 days of exposure to social defeat stress. Males familiar with vanillin sucrose solution showed vanillin sucrose preference while experiencing defeat stress: consumption of vanillin sucrose solution was about 70% of total liquid consumption. However, the consumption of vanillin sucrose solution per gram of body weight in mice exposed to social stress during 20 days was significantly lower than in control males. In the second experiment, males after 8 days of social defeat stress were found to consume significantly less vanillin sucrose solution as compared to control males. On average, during two weeks of measurements, vanillin sucrose solution intake was less than 20% of total liquid consumption in males. Consumption per gram of body weight also appeared to be significantly lower than in control group. The influence of experimental context on the development of anhedonia measured as a reduction of sucrose solution intake by chronically stressed male mice is discussed.

An experimental approach for the study of psychotropic drug effects under simulated clinical conditions.

The sensory contact model can induce various different psychopathological states in male mice (anxious depression, catalepsy, social withdrawal, pathological aggression, cognition disturbances, anhedonia, alcoholism etc.). Additionally, this model facilitates the screening of drugs for therapeutic properties, preventive properties and efficiency under simulated clinical conditions. This approach can reveal the action of drugs at different stages of disease development. It is proposed that this pharmacological approach can be applied for the screening of various novel psychotropic drugs.

Effects of single episodes of severe stress on the behavior of male and female CBA/Lac and C57BL/6J mice.

Experiments were performed to compare the behavior of male and female mice of the inbred strains CBA/Lac and C57BL/6J in the open field test after single episodes of severe stress imposed by forced swimming. Testing was performed 2 h (first test) and one day (second test) after stress. Control animals were intact males and females of these strains, and were also tested in the open field on two sequential days. Both male and female CBA/Lac mice showed increases in the latent period of excursions from the center of the field 2 h after stress. This change persisted to the second test in female CBA/Lac mice. In female C57BL/6J mice, there were changes in four of seven behavioral measures 2 h after stress, though at one day their behavior was as in control individuals. Stress had virtually no effect in males of this strain, only increasing the number of grooming acts in the first test. In addition, detailed analysis of the effects of repeat testing in control and stressed individuals of these mouse strains also revealed interstrain and gender-related differences in the effects of stress. The possible existence of increased basal (trait) and situational (state) anxiety in female C57BL/6J and CBA/Lac mice respectively is discussed.

[Effects of acute and chronic introduction of fluoxetine on anxiety-depressive condition of male and female mice].

The effects of acute and chronic fluoxetine treatment in intact and anxiety-depressive male and female inbred mice of the C57BL/6J strain were studied. The gender differences in the behaviour of mice in the tests estimating anxiety, locomotion and exploration activity, communication, and depressive-like state after fluoxetine injection were established. The dependence of fluoxetine treatment on normal or pathological state in mice was discovered. It was concluded that use of the animals in pathological condition and chronic (but nor acute) fluoxetine treatment are represented as the most correct estimative means of antidepressant efficiency.