Effect of 5-HT2C receptor antagonist RS 102221 on mouse behavior

Injection of RS 102221 (selective antagonist of serotonin 5-HT_2C receptors) in a dose of 2 mg/kg reduced anxiety of mice in the light-darkness test and decreased the amplitude of the startle reflex. RS 102221 in a dose of 1 mg/kg reduced prestimulus inhibition of the startle reflex. No behavioral changes in Porsolt test and motor activity in the open field test were detected. Hence, RS 102221 is characterized by selective anxiolytic activity, and 5-HT_2C receptors are involved in the mechanisms of anxiety and startle reflex formation. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 142, No. 7, pp. 86–89, July, 2006     

UHF-dielectrometry of the urine in prognosis of aggregation stability

The hypothermic effects of 5-HT_1A serotonin receptor agonist 8-OH-DPAT after intranasal, intraperitoneal, and subcutaneous administration were compared. In a dose of 1 mg/kg 8-OH-DPAT induced similar thermal reactions after administration by all three routes. In a dose of 0.5 mg/kg 8-OH-DPAT caused no appreciable changes in body temperature after intraperitoneal injection and decreased it after subcutaneous and intranasal administration. No genotypic differences in the effects of 5-HT_1A receptor agonist administered by different routes were detected in four inbred mouse strains. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 146, No. 10, pp. 413-415, October, 2008     

Effect of Gadolinium Chloride on the Growth and Metastasizing of Lewis Pulmonary Adenocarcinoma in Mice

A single intraperitoneal injection of GdCl₃ in doses of 14 or 28 mg/kg to mice with intravenously transplanted Lewis pulmonary adenocarcinoma on days 3 or 8 after tumor transplantation reduced the mean number of tumor metastases in the lungs. The effect of GdCl₃ was more pronounced if it was injected at the stage of tumor dissemination (day 8). The positive antimetastatic effect of GdCl₃ was presumably due to its capacity to macrophage depression. The direct (not mediated through mononuclear phagocyte system cells) effect of GdCl₃ on tumor cells cannot also be excluded. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 146, No. 11, pp. 548–551, November, 2008     

Testosterone and behavior: Involvement of the hormone in psychotropic effects of baclofen

We studied the effect of baclofen (GABA_B receptor agonist) on the behavior of male mice with different levels of anxiety in tests for social and sexual contact and on blood testosterone levels. The drug reduced testosterone level and behavioral reaction to an unknown male in intact animals and did not modulate the hormone level and social contacts in anxious mice. In the test with receptive female, baclofen reduced testosterone level and sexual motivation in intact males and did not modulate the hormone level and initial sexual interest in anxious mice. Parallelism in the development of behavioral and endocrine components of the reaction to social and sexual stimuli confirms possible involvement of testosterone in psychotropic effects of baclofen. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 2, pp. 222–226, February, 2007     

Naloxone Effects on Behavior of Inbred Mice with Different Response to Emotional Stress in Open Field Test

Effects of nonspecific opiate receptor antagonist naloxone in doses of 0.1, 0.5, 1.0, 5.0, 10.0 mg/kg on open field behavior and spontaneous motor activity were studied in male BALB/c and С57Bl/6 mice. Differently directed effects of naloxone on behavioral parameters of emotional-stress reaction in BALB/c and С57Bl/6 mice were observed. Naloxone increased motor activity in the open field test in BALB/c mice, but decreased it in С57Bl/6 mice. In the absence of stress, naloxone in the studied dose range did not affect spontaneous motor activity in С57Bl/6 mice, and significantly reduced activity in BALB/c mice in doses 0.5 and 1.0 mg/kg.     

Analysis of bromantane pharmacological spectrum

Bromantane (2[n-bromphenyl]aminoadamantane) in doses of 40–60 mg/kg had no effect on spontaneous motor activity of BALB/c mice in a Optovarimex apparatus and prevented freezing in the open field test, but stimulated motor activity in C57B1/6 mice. It is concluded that psychostimulatory and anxiolytic effects are present in the spectrum of the pharmacological activity of bromantane. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 11, pp. 529–531, November, 1999     

Involvement of central and peripheral cannabionoid receptors in the regulation of heart resistance to arrhythmogenic effects of epinephrine

Intravenous injection of the selective cannabinoid receptor agonist HU-210 in doses of 0.05 and 0.25 mg/kg increased heart resistance to arrhythmogenic effects of epinephrine, while intracerebroventricular infusion of this substance had no effect on the incidence of epinephrine-induced arrhythmia. The selective antagonist of type I cannabinoid receptors SR141716A in a dose of 3 mg/kg and ganglion blocker hexamethonium in a dose of 10 mg/kg did not modify the antiarrhythmic effect of HU-210. This effect of HU-210 is probably related to activation of type II peripheral cannabinoid receptors. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 130, No. 11, pp. 552–554, November, 2000     

Comparative study of analgesic potency of ACTH<Subscript>4–10</Subscript> fragment and its analog semax

The effects of ACTH_4–10 fragment and its analog semax on nociception were examined on various animal models. ACTH_4–10 in a dose of 0.5 mg/kg decreased nociception in rats during hindpaw compression test and in mice subjected to acetic acid writhing test. Lower doses of ACTH_4–10 produced no analgesic effect. Semax (0.015–0.500 mg/kg) decreased pain sensitivity in all experimental models. Hence, the substitution of three C-terminal amino acid residues in ACTH_4–10 for Pro-Gly-Pro sequence augmented the analgesic potency of the peptide after its peripheral injection. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 1, pp. 8–12, January, 2007     

Effects of α<Subscript>1</Subscript>-acid glycoprotein on hemostasis in experimental septic peritonitis

Pathogenesis of hemostasis disorders in septic peritonitis and the possibility of their correction with acute phase protein (α₁-acid glycoprotein; two doses of 150 mg/kg) were experimentally studied on outbred albino rats. Platelets count in the peripheral blood and their adhesion to endothelium did not change during peritonitis, while aggregation activity increased due to increased rate and shorter time of aggregation, which was associated with the development of hypercoagulation involving the intrinsic and common coagulation pathways and reduction of antithrombin activity. α₁-Acid glycoprotein increased platelet count above the normal level, normalized aggregation rate, some blood clotting parameters, and antithrombin activity. Hence, α₁-acid glycoprotein is a polyfunctional protein modulating all pathogenetic components in the development of blood clotting disorders during septic peritonitis. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 8, pp. 143–145, August, 2007     

Psychotropic activity of cholecystokinine tetrapeptide analogs

Psychotropic activity of two cholecystokinin analogs Trp-R₁-Asp-Phe-NH₂ and R₂-Trp-R₃-Asp-Phe-NH₂ is studied using behavioral tests. Both analogs have no effect on motor activity. Trp-R₁-Asp-Phe-NH₂ in doses of 0.1 and 0.3 mg/kg exhibits anxiogenic activity and impairs learning (only in a dose of 0.1 mg/kg) of experimental animals. R₂-Trp-R₃-Asp-Phe-NH₂ possesses no anxiogenic activity and in doses of 0.1 and 0.3 mg/kg promotes learning, which attests to its nootropic activity. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 6, pp. 647–650, June, 1998     

Effect of imipramine on the behavior and cerebral 5-HT1A serotonin receptors in mice genetically predisposed to catalepsy

Acute injection of imipramine to NPK mice hereditary predisposed to pinching catalepsy reduced immobility in the forced swimming test, but had no effect on catalepsy. Chronic treatment with imipramine reduced the severity of catalepsy and functional activity of 5-HT_1A serotonin receptors, but did not modify their expression in the hippocampus. NPK mice can be a convenient model for studies of the effects of antidepressant. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 1, pp. 53–55, January, 2006     

The contribution of serotonin 1A receptors to kappa opioid immunosuppression

Activation of kappa opioid receptors (kappa-OR) with the selective agonist rimorphin (0.1 mg/kg) produced marked suppression of the immune response in CBA mice. This effect was not seen on administration of rimorphin on the background of a reduction in the activity of the serotoninergic (5-HTergic) system resulting from stimulation of presynaptic (8-OH-DPAT, 0.1 mg/kg) or blockade of postsynaptic (WAY-100635, 1.0 mg/kg) 5-HT_1A receptors. These data led to the conclusion that 5-HTergic mechanisms involving preand postsynaptic 5-HT_1A receptors have a role in kappa-opioid-mediated immunosuppression. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 94, No. 7, pp. 807–813, July, 2008.     

Differential involvement of central 5-HT<Subscript>1B</Subscript> and 5-HT<Subscript>3</Subscript> receptor subtypes in the antinociceptive effect of paracetamol

Objective: We investigated the effect of pre-treatment with ondansetron or CP 93129 (a 5-HAT_1B agonist) on the antinociceptive activity of paracetamol and the changes in central 5-HT₃ receptors induced by paracetamol alone or co-administered with ondansetron.Materials and Subjects: Male Wistar rats (eight per group) were injected with ondansetron (2 and 4 mg/kg s.c.) or CP 93129 (0.5, 1 and 2 mg/kg s.c.) 15 min before paracetamol (400 mg/kg, i.p.).Methods: Pain threshold was evaluated in the hot-plate or in the paw pressure test 30 min after the last treatment. 5-HT₃ receptor binding capacity was measured in the frontal cortex, temporal-parietal cortex and midbrain by means of radioligand binding technique. Statistical analysis was done using ANOVA followed by Student-Newman-Keuls test and 2 X 2 factorial analysis when appropriate.Results: Pre-treatment with ondansetron, at doses of 2 and 4 mg/kg, did not affect the antinociceptive activity of paracetamol in the hot-plate test and in the paw pressure test. Paracetamol did not change the characteristics of 5-HT₃ receptors in all the areas investigated. Ondansetron (4 mg/kg s.c) per se significantly increased the 5-HT₃ receptor number in the areas used, the effect not being modified by co-administration with paracetamol. On the other hand, CP 93129 (2 mg/kg s.c.) significantly prevented the effect of paracetamol in both algesimetric tests used.Conclusions: Our data indicate that 5-HT_1B but not 5-HT₃ receptors are involved in the antinociceptive effect of paracetamol in our experimental conditions.Received 25 November 2002; returned 10 April 2003; accepted by G. Geisslinger 22 April 2003     

Immunocorrecting properties of GB-115 dipeptide

We studied the effects of a new dipeptide with anxiolytic activity (GB-115, N-phenylhexanoyl-glycyl-L-tryptophan amide) on parameters of the immune in intact mice and in animals with secondary immunodeficiency caused by cyclophosphamide. GB-115 in doses of 0.1–10 mg/kg stimulated phagocytic activity of peritoneal macrophages and humoral immune response in intact mice. GB-115 exhibited immunocorrecting activity in animals with secondary immunodeficiency. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 5, pp. 548–551, May, 2008     

Significance of initial emotional state for neuroimmunomodulation in conditions of activation and blockade of 5-HT1A receptors

Experiments performed on male CBA mice immunized with sheep erythrocytes at a dose of 5·10⁸ cells showed that the selective agonist of serotonin 5-HT_1A receptors 8-OH-DPAT (1 mg/kg) suppresses the immune response in aggressive animals. In mice demonstrating the submissive type of behavior, formed during 10 days of experience of defeats, activation of 5-HT_1A receptors with 8-OH-DPAT had no effect on the immune response. However, treatment with the selective 5-HT_1A receptor blocker WAY-100635 stimulated the immune response, but only in submissive mice. These data lead to the conclusion that activation and blockade of 5-HT_1A receptors have different effects on the immune response in CBA mice depending on the initial emotional state of the animals, due to different activities of neurotransmitter systems, particularly the serotoninergic, in aggressive and submissive mice. __________ Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 55, No. 4, pp. 567–572, July–August, 2005.     

Activation of maternal behavior of albino rats after combined treatment with dopamine and opioid receptor antagonists in low doses

We studied the effect of D1/D2 antagonist haloperidol on maternal motivation in nursing albino rats. Haloperidol in a dose of 0.2 mg/kg significantly attenuated parental reactions and motor and exploratory activities. In a lower dose (0.1 mg/kg) the drug produced the same effect on maternal behavior (number of approaches to newborns) without reducing motor activity. The effect of low-dose haloperidol was different after naloxone treatment (0.2 mg/kg intranasally): the number of pup transfers increased significantly. The detected phenomenon indicates good prospects of combined treatment with agents modifying the cerebral dopaminergic and opioid systems as the method for correction of disorders in maternal behavior. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 142, No. 8, pp. 124–127, August, 2006     

Effects of semax against the background of dopaminergic receptor blockade with haloperidol

We studied the neurotropic effects of ACTH(4–10) analog semax against the background of dopaminergic receptors blockade with haloperidol. Intranasal administration of semax (0.05, 0.2, and 0.6 mg/kg) produced virtually no effect on disturbances of orientation and exploratory reactions and motor activity caused by intraperitoneal injection of 0.2 mg/kg haloperidol. By contrast, preliminary administration of 0.05 mg/kg semax prevented haloperidol-induced disturbances in active avoidance conditioning. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 2, pp. 128–132, February, 2006     

Functional activity of 5-HT4 receptors in children with congenital heart disease

The effect of 5-methoxytryptamine (5-HT₄ receptor agonist) on the inotropic function of atrial myocardium was studied in children aged 2 months to 17 years, operated on for congenital heart disease. Functional activity of 5-HT₄ receptors was 8.4 times higher in dysfunction of the atrial septum in comparison with other congenital heart diseases. The positive inotropic effects of 5-HT₄ receptor agonist can promote compensation of myocardial work in children with pathological circulation. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 142, No. 12, pp. 675–677, December, 2006     

Inversion of the response to serotonin in rats with traumatic shock

Normally serotonin reduced blood pressure. It was shown that in rats with traumatic shock its hypotensive effect was transformed into hypertensive one. In vitro serotonin exhibited a slight vasoconstrictor effect on isolated rat aorta, while 24 h after injury, the strength of aortic contractions in response to serotonin increased 2.2 times. Desensitization of glucocorticoid receptors caused by injection of high doses of dexamethasone (3 mg/kg) to rats for 5 days led to similar changes in serotonin effect. We hypothesized that inversion of the response to serotonin in shock was caused by increased activity and/or expression of vasoconstrictor serotonin receptors in blood vessels. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 3, pp. 266–269, March, 2008     

Toxicity,analgesic and anti-inflammatory activities of tectorigenin

Abstract

Objective: Belamcanda chinensis has been used in oriental medicine for the treatment of inflammatory diseases. Tectorigenin is a main compound in B. chinensis and possess inhibitory activity against inflammatory responses. Thus, the current study aimed at evaluating toxicity as well as analgesic and anti-inflammatory effects of tectorigenin in animal models.

Methods: Tectorigenin was employed to evaluate acute and subacute toxicity. Acetic acid-induced writhing in mice was used for analgesic test. The anti-inflammatory activity was tested in carrageenan-induced paw edema.

Results: LD₅₀ of tectorigenin was 1.78?g/kg p.o. in mice and no toxic symptoms were observed at doses up to 300?mg/kg in a subacute toxicity test during 28-day treatment. Tectorigenin at doses of 50 and 100?mg/kg had an analgesic effect on acetic acid-induced acute visceral pain in mice. In inflammatory rat model, tectorigenin at 60?mg/kg significantly reduced carrageenan-induced edema.

Conclusion: We demonstrated that tectorigenin is a safe and promising analgesic and anti-inflammatory agent.