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.

[Serotonergic genes in the development of anxiety/depression-like state and pathology of aggressive behavior in male mice: RNA-seq data].

In course of daily agonistic interactions, mice tend to stratify into those with chronic social defeats and those that repeatedly display aggression, which lead to the development of mixed anxiety/depression-like state and the pathology of aggressive behavior, respectively. Using the data of whole transcriptome analysis (RNA-seq), the changes in the expression of serotonergic genes involved in the synthesis, inactivation, and reception of serotonin, as well as of the Creb1 (transcription factor) gene and the Bdnf (brain-derived neurotrophic factor) gene were detected in the striatum (STR), ventral tegmental area (VTA), midbrain raphe nuclei (MRN), hypothalamus (HYP), and hippocampus (HIP) of defeated and aggressive male mice. In mice of both groups, the Tph2, Ddc, Slc6a4, Htr2a, Htr3a, Htr5b, Slc18a2, and Bdnf genes were downregulated in the MRN and the Tph2, Ddc, and Slc6a4 genes were upregulated in the VTA. These changes were more significant in defeated mice. The Htr5b gene has first been shown to be involved in mechanisms of depression and pathology of aggressive behavior. In the defeated mice, the expression levels of the Htr4 and Aldh1b1 genes were increased in the MRN, and expression levels of the Maob, Htr4, Htr1a, and Slc18a2 genes were increased in the VTA, while the expression level of the Htr3a gene was decreased. In the HYP of aggressive mice the Maoa, Htr2a, Htr2c, and Creb1 genes were downregulated and the Htr6 gene was upregulated. In the defeated mice, the Maoa and Creb1 genes were downregulated and the Htr6 and Aldh1b1 genes were upregulated in the HYP. In the STR, the Htr1a gene was downregulated and the Htr7 and Bdnf genes were upregulated. The Htr1b gene was upregulated in the HIP. The coexpression of dopaminergic and serotonergic genes in the MRN and VTA in the control of pathological behaviors is discussed. Thus, the complex pattern of differential expression of serotonergic genes in brain regions developing under repeated agonistic interactions in mice in dependence on behavioral pathology have been observed.

[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 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.

Behavioral characteristics of mice with genetic knockout of monoamine oxidase type A.

Transgenic mice of line Tg8 were used to study the effects of deletion of the monoamine oxidase type A gene and the absence of the corresponding enzyme on behavior. These experiments showed that Tg8 mice with genetic knockout of monoamine oxidase type A differed from mice of the parental line C3H/HeJ by lower levels of the startle reflex in response to an acoustic signal, while there was no difference in the prestimulus inhibition of the startle response. Tg8 mice showed decreased investigative activity and decreases in the number of sector crossings in the light-dark anxiety test. There were significant increases in aggression as a motivation in male Tg8 mice, which was manifest as an increase in the number of mice demonstrating aggression and a decrease in the latent period of attack. The intensity of aggression changed to a lesser extent - the number of fights even decreased, though longer periods of keeping mice together resulted in increased numbers of deaths among intruder mice. At the same time, there were no significant differences between mice with genetic knockout of monoamine oxidase type A and control mice in terms of the expression of sexual activation: the behavioral responses of Tg8 males to presentation of females was marked and was no different from that of male C3H/HeJ mice. Knockout of the gene had no effect on movement activity on behavior in an elevated cross-shaped maze or in the test for predisposition to catalepsy.

Altered behavior and alcohol tolerance in transgenic mice lacking MAO A: a comparison with effects of MAO A inhibitor clorgyline.

The influence of deficiency of monoamine oxidase A (MAO A) gene and the lack of enzyme MAO A on the behavior of transgenic mouse strain (Tg8) was studied. It was shown that MAO-A-lacking mice differed from mice of the wild-type strain C3H/HeJ (C3H) by an attenuated acoustic startle response, prepulse inhibition (PPI) was unchanged. In Tg 8 mice, the exploratory nose-poking in the holeboard test as well as exploratory line crossing in the "light-dark" test were decreased. No effect of MAO A deficiency on locomotor activity was found. No alcohol preference or difference between Tg8 and C3H in ethanol consumption in the free-choice test has been found, although an increase in alcohol tolerance has been demonstrated. Ethanol-induced (0.3 g/100 g ip) sleep latency was longer, duration of sleep was shorter and ethanol hypothermia was reduced in MAO-A-lacking mice. Comparison of effects of MAO A knockout with those of irreversible MAO A inhibitor clorgyline (5 and 10 mg/kg ip) on C3H mice showed a similar reducing effect on ethanol-induced sleep, but potentiated ethanol-induced hypothermia. Clorgyline administration provoked a tendency to decrease of exploratory activity in the nose-poking test and decreased the frequency of exploratory rearings in the light-dark test. Clorgyline (5 and 10 mg/kg) did not affect the acoustic startle response, but a dose of 5 mg/kg diminished PPI. Therefore, Tg8 mice exhibited a decreased startle response and exploratory activity and an increased tolerance to ethanol. A similar increase in tolerance to ethanol-induced sleep and a tendency to decrease exploratory behavior were displayed by clorgyline. Other effects on behavior were different, suggesting the influence of long-lasting action of MAO A knockout and the involvement of a compensatory mechanism in Tg8 mice.