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The effect of 5-HT 1A receptor agonist 8-OH-DPAT (intraperitoneal injection in doses of 1, 2, and 4 mg/kg) on spontaneous alternation behavior of mice in Y-maze was studied without and with habituation procedure and food reward. In the first case, 8-OH-DPAT administration led to a decrease in spontaneous alternation and locomotor activity in mice. At the same time, 8-OH-DPAT treatment after habituation and food deprivation increased repeated choices of goal arms without affecting locomotor activity, which was consistent with perseverative behavior. 8-OH-DPAT-induced decrease in spontaneous alternation behavior in Y-maze in mice with habituation and food reward is the most suitable procedure for experimental modeling of the perseverative behavior and studying the anticompulsive activity of new substances., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

The strategy of glaucoma therapy is aimed at preserving visual functions and ensuring an acceptable quality of life for patients. To achieve this strategic goal, clinicians in their practice use drugs that affect the main factor in the progression of the disease - intraocular pressure (IOP), aiming to reduce it to an individual target level. It is not always possible to achieve optimal IOP values with monotherapy. Many patients require a combination of drugs from different pharmacological groups. Xalacom is a fixed drug with good tolerability and t hypotensive effect. This review focuses on the benefits of this drug for the treatment of glaucoma.

Induction of BDNF-TrkB signaling is associated with the action mechanisms of conventional and fast-acting antidepressants. GSB-106, developed as a small dimeric dipeptide mimetic of BDNF, was previously shown to produce antidepressant-like effects in the mouse Porsolt test, tail suspension test, Nomura water wheel test, in the chronic social defeat stress model and in the inflammation-induced model of depression. In the present study, we evaluated the effect of chronic per os administration of GSB-106 to Balb/c mice under unpredictable chronic mild stress (UCMS). It was observed for the first time that long term GSB-106 treatment (1 mg/kg, 26 days) during ongoing UCMS procedure ameliorated the depressive-like behaviors in mice as indicated by the Porsolt test. In addition, chronic per os administration of GSB-106 resulted in an increase in BDNF levels, which were found to be decreased in the prefrontal cortex and hippocampus of mice after UCMS. Furthermore, prolonged GSB-106 treatment was accompanied by an increase in the content of pTrkB 706/707 in the prefrontal cortex and by a pronounced increase in the level of pTrkB 816 in both studied brain structures of mice subjected to UCMS procedure. In summary, the present data show that chronic GSB-106 treatment produces an antidepressant-like effect in the unpredictable chronic mild stress model, which is likely to be associated with the regulation of the BDNF-TrkB signaling.

Micro-CT visualization allows reconstruction of eye structures with the resolution of light microscopy and estimation of tissue densities. Moreover, this method excludes damaging procedures and allows further histological staining due to the similar steps in the beginning. We have shown the feasibility of the lab-based micro-CT machine usage for visualization of clinically important compartments of human eye such as trabecular outflow pathway, retina, iris and ciliary body after pre-treatment with iodine in ethanol. We also identified the challenges of applying this contrasting technique to lens, cornea, and retina and proposed alternative staining methods for these tissues. Thereby this work provides a starting point for other studies for imaging of human eyes in normal and pathological conditions using lab-based micro-CT systems., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

We studied the influence of intraperitoneal injection of ATP-sensitive potassium channels inhibitor glibenclamide in doses of 0.01, 0.1, 1, and 10 mg/kg on the effects of a new pyrazolo[C]pyridine derivative GIZh-72 (4,6-dimethyl-2-(4-chlorphenyl)-2,3-dihydro-1Hpyrazolo[ 4,3-C]pyridine-3-on, chloral hydrate; 20 mg/kg, intraperitoneally) in the marble burying and open-field tests in mice. It was found that glibenclamide produced an anxiolytic effect in the open-field test (in a dose of 0.01 mg/kg) and anticompulsive effect in the marble burying test (in doses of 1 and 10 mg/kg). The observed behavioral effects of glibenclamide did not depend on blood glucose level. At the same time, glibenclamide in subeffective (0.01 and 0.1 mg/kg) and effective (1 and 10 mg/kg) doses potentiated the psychotropic effects of GIZh-72 in these tests. It can be assumed that the psychotropic effects of GIZh-72 depend on functional activity of ATP-sensitive potassium channels.

Standard water-reinforced drug discrimination model was employed to train Wistar rats to discriminate the intraperitoneal injections of tricyclic antidepressant amitriptyline (5.4 mg/kg) and physiological saline. To examine the role of GABA A receptors in psychotropic action of amitriptyline, the substitution tests were performed with muscimol (0.1-1.0 mg/kg) and pregnenolone (30-50 mg/kg). Similar tests were carried out with amitriptyline interoceptive antagonists bicuculline (1 mg/kg), flumazenil (15 mg/kg), finasteride (5 mg/kg), and indomethacin (7.5 mg/kg). The study showed that interoceptive effects of amitriptyline depend on functional activity of GABA A receptors but not on the neurosteroid site of GABA A receptor complex.

The behavioral and neurochemical effects of amitriptyline (10 mg/kg, i.p.) and fluoxetine (20 mg/kg, i.p.) after single and chronic administration in the setting of unpredictable mild stress in outbred ICR (CD-1) mice were studied. After a 28-day exposure to stress, we observed an increase in depressive reaction in a forced swim test in mice, as well as reduced hippocampal levels of serotonin (5-hydroxytryptamine, 5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) and an increased hypothalamic level of noradrenaline (NA). Single and chronic administration of amitriptyline and fluoxetine shortened the immobility period and increased the time corresponding to active swimming in the forced swim test. The antidepressant-like effect of fluoxetine - but not of amitriptyline - after a single injection coincided with an increase in the 5-HT turnover in the hippocampus. Chronic administration of the antidepressants increased the hypothalamic levels of NA. Thus, the antidepressant- like effect of amitriptyline and fluoxetine may result from an enhancement of the stress-dependent adaptive mechanisms depleted by chronic stress., (Copyright ® 2020 National Research University Higher School of Economics.)

The antidepressant-like effect of fluoxetine (20 mg/kg i.p.) has been assessed using the forced swimming test (FST) in IRC (CD-1) mice exposed or not to a pretest session of different duration (5 or 20 min). The influence of the mitochondrial translocator protein (TSPO) activity on the antidepressant-like effect of fluoxetine (20 mg/kg i.p.) in the FST was also studied. The antidepressant-like effect of fluoxetine was observed only in mice subjected to a 5-min pretest session 24 h before the FST. The TSPO antagonist PK11195 [1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide; 1 or 3 mg/kg i.p.] inhibited the antidepressant activity of fluoxetine in the FST. In the present study, fluoxetine or PK11195 was administered for a short duration. We suppose that the functional activity of TSPO may depend on a pretest session and that using this procedure is necessary to detect antidepressant activity of fluoxetine-like drugs.

The anxyolitic effects of diazepam and afobazole on the anxiety model caused by subconvulsive doses of pentylenetetrazole have been studied in the open field test and drug discrimination in rodents. It is found that diazepam (I and 5 mg/kg, i.p.) and afobazole (1 mg/kg, i.p.) reduced the pentylenetetrazole-induced (20 mg/kg, i.p.) anxiety in Wistar rats in the open field test. Only diazepam (1 mg/kg, i.p.) in Balb/c mice and only afobazole (1 mg/kg, i.p.) in C57B11/6 mice decreased anxiety caused by pentylenetetrazole (30 mg/kg, i.p.). Afobazole (20 mg/kg, i.p.) partially inhibited the effect of pentylenetetrazole (20 mg/kg, i.p.) in drug discrimination paradigm in Wistar rats learned in the Skinner box, in contrast to diazepam (5 mg/kg, i.p.) that fully blocked the stimulus properties of non-competitive GABA(A) receptor antagonist. The obtained results suggest that restorative effects of diazepam and afobazole on pentylenetetrazole-induced anxiety depend on the type of emotional stress reaction in rodent species and mice strains, though anxiogenic effects of pentylenetetrazole are not influenced by interstrain differences.

It was studied the anxiolytic properties of 4,6-dimethyl-2-(4-chlorophenyl)-2,3-dihydro-1Í-pyrazolo[4,3-c]pyridin-3-one chloralhydrate (GIZh-72, 20 mg/kg, i.p.) and afobazole (1 mg/kg, i.p.) in comparison to fluoxetine (20 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.) in open-field and marble burying tests on male mice of inbred strains BALB/C and C57BL/6. It is established that GIZh-72 administered both 30 min and 24 h before testing produces anxiolytic effect in the open-field test. The open field anxiety response patterns following GIZh-72 administration differed from these in diazepam or afobazole treated BALB/C mice. This drug also decreased the number of buried marbles in both BALB/C and C57BL/6 mice, the effect being comparable to that of afobazole and fluoxetine. In operant drug discrimination liquid-reinforcement paradigm in male Wistar rats, GIZh-72 failed to antagonize or substitute for the interoceptive stimulus cues of pentylenetetrazole evoking the saline-like responses in the latter case, which was evidence for the absence of properties of a ligand bearing positive modulator sites of GABA-A receptor.

The mechanism of the photodegradation of azo dyes via ultrasonication is studied using a combination of the high-performance liquid chromatography and UV-vis spectroscopy with detailed analysis of the kinetics. Based on the kinetics studies of the sonodegradation, it was proposed that the degradation of azo dyes was a multistage process that involved: (1) the direct attack of azo bonds and phenyl rings of dyes by the sonochemically formed reactive oxygen species; (2) the activation of semiconductor particles by the light emitted during cavitation and the triggering of the photocatalytic pathways of dye degradation and (3) increase of the adsorption capacity of the semiconductor particles due to the sonomechanically induced interparticle collisions. The detailed kinetics study can help in following an effective process up-scaling. It was demonstrated that extremely short pulses of light flashes in a cavitated mixture activated the surface of photocatalysts and significantly enhanced dye degradation processes., (© 2014 The American Society of Photobiology.)

The role of GABA-A receptors in psychotropic effects of pyrrolo[1,2-a][1,4]diazepine derivatives GMAL-24 and GMAL-27 has been studied on an operant method with liquid reinforcement of drug discrimination in male Wistar rats. It is established that, in substitution tests, GMAL-24 (2, 5, 10 mg/kg) and GMAL-27 (2, 5, 10 mg/kg) do not produce interoceptive effects of phenazepam (1 mg/kg) and fail to inhibit interoceptive effects of corasol (20 mg/kg). The obtained results indicate that pyrrolo[1,2-a][1,4]diazepine derivatives do not exhibit GABA-A receptor-positive modulator properties in vivo.

Interoceptive stimulus properties of amitriptyline (54 mg/kg body weight), fluoxetine (10 mg/kg), and pyrrolo[1,2-a][1,4]diazepine derivative GMAL-24 (10 mg/kg) were studied in a standard operant model with liquid reinforcement of drug discrimination (DD) in male Wistar rats. A new experimental schedule that includes subchronic (7-day) administration of a training drug was used to perform DD learning. For the first time, it was found that amitriptyline has a discriminative interoceptive stimulus properties. Neither fluoxetine nor GMAL-24 did exhibit interoceptive properties. Imipramine (15 mg/kg, i.p.) fully substitutes for amitriptyline stimulus in substitution test. Fluoxetine (5 - 20 mg/kg, i.p.) failed to substitute with amitriptyline. Thus, amitriptyline/saline drug discrimination should be used for a comparative analysis of the central mechanisms of action of psychotropic substances, rather than for screening specific antidepressant activity.

We studied plus-maze behavior of inbred Krushinskii-Molodkina, Wistar, and black-hooded rats (originating from the Long-Evans outbred strain) differing by predisposition to audiogenic seizures. The severity of audiogenic seizures partially correlated with anxiety and negatively correlated with the total level of locomotor activity in the elevated plus-maze. The anxiety parameters in Krushinskii-Molodkina rats were evaluated after injection of anticonvulsant levetiracetam and anxiolytic afobazol. Levetiracetam and afobazol somewhat stimulated locomotor activity.

Interoceptive effects of afobazole (20 mg/kg, i.p.) and diazepam (0.5 and 5.0 mg/kg, i.p.) have been investigated using operant drug discrimination (DD) and passive avoidance "step through" state dependent dissociative learning (DL) paradigms in male autobred rats. It is established that afobazole in contrast to classical anxiolytics (diazepam) does not produce the state dependence (DL and DD). In substitution tests, afobazole (20 mg/kg, i.p.) caused saline level responding in diazepam-trained rats and did not influence the general profile of interoceptive diazepam stimulus. The data suggest the absence of overlap in receptor mechanisms of the interoceptive effects of afobazole and diazepam and low probability of drug dependence development after long-term (clinical) afobazole treatment.

A possibility is discussed of use of methods of non-linear dynamics for analysis of spontaneous EEG and if the EEG caused by low acoustic stimuli in healthy people and in patients with epilepsy. A use of methods of non-linear dynamics--the fractal dimension of EEG--in clinical practice and in research is described.

Ultrasound examination using color Doppler imaging was used in 70 patients with non-epithelial ovarian carcinoma and 23 patients with subserous nodes of uterine myoma. Diagnosis was confirmed by histological assay of resected material. The procedure can be used for differentiated diagnosis between non-epithelial ovarian carcinoma and subserous nodes of uterine myoma, as well as for appraisal of individual features of tumor so that adequate treatment might be selected.

Clinico-morphological examination of adult granulosa cell tumors of the ovary was carried out in 17 patients (mean follow-up duration--146.2 +/- 22.16 months). Overall and relapse-free survival appeared significantly higher in low expression of Ki-67 (8.63 +/- 1.4%), mutant suppressor gene p53 (3.55 +/- 1.9%) and low mitotic levels in tumor (2.33 +/- 0.9 per 10 fields of microscope) (p < 0.05).

The product of melatonin oxidation, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), was synthesized and a method for its determination in biological samples was developed. High performance liquid chromatography (HPLC) with fluorescence detection provided good sensitivity and selectivity. Wavelengths of 350 and 480 nm were used for excitation and emission, respectively. Serum and retinal homogenates were extracted with chloroform prior to analysis by HPLC. Endogenous AFMK was detected in the retina of rats but the serum concentration of this melatonin metabolite was below the detection limit of the method for measurement. Retinal AFMK concentration was higher during the dark phase of the light/dark cycle, when the retinal melatonin content is maximal. Intraperitoneal administration of melatonin significantly increased serum and retinal AFMK levels. Formation of AFMK from melatonin was also confirmed by in vivo microdialysis with the probe implanted into the brain lateral ventricle. The study shows that AFMK is indeed a product of melatonin oxidation in vivo. The possible physiological significance of melatonin oxidation metabolic pathway is discussed.