Specifics of Experimental Modeling 8-OH-DPAT-Induced Perseverative Behavior in Mice.

The effect of 5-HT1A 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.

[Xalacom: possibilities and advantages of the drug in the treatment of patients with glaucoma]. / Ksalakom: vozmozhnosti i preimushchestva preparata v terapii glaukomy.

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.

The Behavioral and Neurochemical Aspects of the Interaction between Antidepressants and Unpredictable Chronic Mild Stress.

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.

Psychotropic Effects of a New Pyrazolo[C]Pyridine Derivate GIZh-72 are Related to Functional Activity of Atp-Sensitive Potassium Channels.

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.

Role of GABAA Receptors in the Mechanism of In Vivo Psychotropic Activity of Amitriptyline in Rats.

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 GABAA 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 GABAA receptors but not on the neurosteroid site of GABAA receptor complex.

ANXIOLYTIC EFFECTS OF DIAZEPAM AND AFOBAZOLE ON THE ANXIETY RESPONSE EVOKED BY GABA(A) RECEPTOR BLOCKADE IN WISTAR RATS AND INBRED MICE OF Balb/c AND C57BI/6 STRAINS.

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.

[THE STUDY OF ANXIOLYTIC PROPERTIES OF NEW PYRAZOLO[C]PYRIDINE DERIVATIVE GIZH-72].

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.

[Comparative study of discriminative stimulus properties of antidepressants].

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.

[Role of GABA-A receptors in mechanism of psychotropic action of pyrrol[1,2-a][1,4]diazepines studied using drug discrimination technique in Wistar rats].

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.

Anxiety and predisposition to audiogenic epilepsy in rats of different genotypes.

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.

[Methods of non-linear dynamics in estimation of electroencephalograms of healthy people and of patients with epilepsy].

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.

[Comparative study of the interoceptive effects of afobazole and diazepam].

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.

[Features of ultrasound diagnosis of non-epithelial ovarian carcinoma].

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.

[The role of Ki-67, mutant suppressor gene p53 and low mitotic levels in defining the prognosis for adult granulosa cell tumor of the ovary].

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).