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     

Endogenous dipeptide cycloprolylglycine shows selective anxiolytic activity in animals with manifest fear reaction

Experiments on two mouse strains with opposite reactions to emotional stress showed selectivity of the anxiolytic effect of endogenous dipeptide cycloprolylglycine. In the open field test cycloprolylglycine (0.01-0.10 mg/kg intraperitoneally) dose-dependently (1.8-2.1-fold) increased motor activity of BALB/c mice with manifest fear reaction and had no effect on C57Bl/6 mice with active behavior. The content of endogenous cycloprolylglycine in mouse brain correlated with the type of emotional stress reaction: its content in the brain of C57Bl/6 mice 1.5 times surpassed that in BALB/c mice. It is concluded that cycloprolylglycine is involved in the endogenous regulation of fear reaction.     

Psychotropic Effects of Sidnocarb and Ladasten in Inbred Mice with Different Reaction to Emotional Stress

Dose-dependent relationship of the effects of sidnocarb and Ladasten on open field behavior and free motor activity was studied in inbred C57Bl/6 and BALB/c mice differing by emotional stress reaction phenotype. Ladasten in a dose of 10 mg/kg produced activating and anxiolytic effects on BALB/c mice in the open field test. Combined injection of Ladasten (10 mg/kg) and sidnocarb (6 or 12 mg/kg) activated animal behavior in both tests.__________Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 139, No. 3, pp. 316–318, March, 2005     

Effect of dioxydine and cyclophosphane on lipid peroxidation and superoxide dismutase and catalase activities in C57Bl/6 and BALB/c mice

Twenty-four hours after intraperitoneal injection of cyclophosphane (40 mg/kg) and dioxydine (300 mg/kg) to C57Bl/6 mice, liver catalase activity dropped by 29 and 23%, respectively. In BALB/c mice, dioxydine (but not cyclophosphane) reduced catalase activity by 24%. Superoxide dismutase activity was lowered by cyclophosphane (but not dioxydine) in BALB/c mice, and by both dioxydine and cyclophosphane in C57Bl/6 mice (by 24 and 86%, respectively). The level of 2-thiobarbituric acid (TBA)-reactive lipid peroxidation (LPO) products in the liver of BALB/c mice treated with cyclophosphane and dioxydine increased 1.4- and 2.1-fold, respectively, while in C57Bl/6 mice it did not differ from the control. The initial rate ofin vitro-induced LPO in BALB/c mice receiving cyclophosphane and dioxydine increased 1.5- and 4-fold, respectively. In C57Bl/6 mice both cyclophosphane and dioxydine inhibited the accumulation of TBA-reactive LPO products. On the whole, animals of the C57Bl/6 strain are more resistant to the LPO-inducing action of mutagens than BALB/c mice, despite the fact that the latter are characterized by a higher activity of antioxidant enzymes. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, No. 5, pp. 528–532, May, 1996     

Benzodiazepine Reception in C57Bl/6 and BALB/c Mice Depending on the Type of Stress Factor

Specific binding of ³Н-fl unitrazepam with synaptosomal membranes after exposure to open field test and “contact with predator” test was measured in C57Bl/6 and BALB/c mice. Stress-induced decrease in benzodiazepine binding after open field test was observed only in BALB/c mice and after contact with predator in both animal strains.     

Effect of psychotropic drugs on behavior of inbred mice under emotional stress

The behavior of C57BL/6, CBA, and BALB/c mice in an open field test was studied after administration of phenazepam in doses of 0.05, 0.075, and 0.1 mg/kg and of sydnocarb in doses of 6, 12, and 24 mg/kg. The initial response to emotional stress was characterized by greatest motor activity (MA) in C57BL/6 mice and minimal in BALB/c mice. Phenazepam lowered MA in C57BL/6 mice proportionally to the dose. A biphasic effect of the tranquillizer was found in BALB/c mice. Depending on the dose, sydnocarb stimulated MA of C57BL/6 mice, did not effect the behavior of CBA mice, and in a dose of 24 mg/kg, it increased MA of BALB/c mice.Laboratory of Pharmacological Genetics, N. I. Pirogov Second Moscow Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 7, pp. 38–40, July, 1979.     

Morphofunctional characteristic of the immune system in BALB/c and C57BL/6 mice

Inbred animals serve as an adequate model to study the role of genetic factors in adaptive, disadaptive, and pathological processes. Morphofunctional study of the immune system was performed on intact BALB/c and C57Bl/6 mice. The structural and functional parameters of the immune system in BALB/c and C57Bl/6 mice differ under physiological conditions. In BALB/c mice, volume density of T zone in the spleen and production of IL-2, IL-3, IL-4, IL-10, and TNF-α were much higher than in C57Bl/6 mice. However, IL-12 production in BALB/c mice was lower than in C57Bl/6 mice. C57Bl/6 mice were characterized by higher cytostatic activity of splenic NK cells. The observed interstrain differences are genetically determined and contribute to the type of adaptive processes and different sensitivity of these mice to pathogenic agents.     

Systemic administration of naloxone produces analgesia in BALB/c mice in the formalin pain test

Systemic administration of naloxone usually produces either hyperalgesia or no change in nociception depending on the animal species used and/or the pain test employed. This study, however, demonstrates that naloxone produces a dose-dependent analgesia in the formalin pain test using an inbred strain of albino mouse. Female BALB/c, C57BL/6 and CD1 mice were injected subcutaneously with naloxone HCl in saline (0.1 10.0 mg/kg) or saline alone, and tested for analgesia using the formalin test. Naloxone produced a statistically significant dose-dependent analgesia in the BALB/c mice, with an ED50 of 0.24 mg/kg and almost total analgesia at doses of 1 mg/kg or greater. No changes in pain behaviour were observed in the C57BL/6 or CD1 strains of mice. We believe this to be the first report of analgesia following administration of doses of naloxone normally used for opioid antagonism. To determine if this effect was specific to the formalin test, the 3 strains of mice were injected subcutaneously with naloxone HCl and tested in the tail-flick test. Naloxone had no analgesic action in this test in any of the strains.     

Immunity Parameters in Mice of Different Strains

Quantitative composition and functional activity of immunocompetent cells differ in mice of different strains. The counts of T cells in the bone marrow and spleen, proliferative activity of T cells in the spleen, levels of IL-2 and IL-10 production by splenic T cells, number of antigen-specific T cells and their functional activity are low in C57Bl/6, BALB/c, and CC57W mice and high in CBA/CaLac, DBA/2, and C3H animals. Low phagocytic activity of peritoneal macrophages was detected in BALB/c and CC57W mice and high activity in C3H animals. The content of antibody-producing cells in the spleens of C57Bl/6, BALB/c, and CC57W mice is higher than in CBA/CaLac, DBA/2, C3H, A/SN, and AKR/JY mice. Functional activity of B cells is lower in BALB/c and CC57W compared to CBA/CaLac and DBA/2 mice. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 140, No. 8, pp. 189–191, August, 2005     

Morphofunctional characteristic of mast cells in BALB/c and C57Bl/6 mice during cold exposure

Mast cells of the mesentery and subcutaneous tissue in BALB/c and C57Bl/6 mice were studied after single and repeated cold exposure (−20°C, 3 min). Immediate adaptive reactions of mast cells in BALB/c and C57Bl/6 mice did not differ after single cold exposure and were manifested in increased degranulation. Repeated cold exposure of BALB/c mice was followed by an adaptive reaction, which included an increase in the count of mast cells in subcutaneous tissue and normalization of the degranulation index. In C57Bl/6 mice the count of mast cells in subcutaneous tissue decreased, while the degranulation index remained high. These changes reflect the disadaptive response of mast cells to repeated cold exposure. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 8, pp. 207–209, August, 2004     

Effect of 5HT2C-receptor agonist MK-212 on blood corticosterone level and behavior in mice

A dose-dependent the effect of 5HT_2C-receptor agonist MK-212 on mouse behavior was demonstrated. Intraperitoneal injection of MK-212 in high doses (0.5 and 1.0 mg/kg) increased blood level of corticosterone in mice and reduced their motor activity. In low doses of 0.1 and 0.2 mg/kg, the agonist reduced anxiety, but had no effect on motor activity. It is hypothesized that low doses of MK-212 exhibited anxiolytic activity in mice. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 142, No. 11, pp. 541–544, November, 2006     

Genotype-dependent characteristics of behavior in mice in cognitive tests. The effects of Noopept

Male C57BL/6J, BALB/c, and DBA/2J mice showed differences in their abilities to perform two cognitive tests. C57BL/6J mice had good learning ability and memory trace retention (at 10 days) in a simplified Morris maze, while BALB/c mice had low levels of memory trace retention and DBA/2J mice had low learning ability in this test. I.p. administration of the nootropic agent Noopept (GVS-111, N-phenylacetyl-L-prolylglycine ethyl ester) at a dose of 0.5 mg/kg 15 min before the start of the test induced significant improvements in long-term memory in this test in BALB/c mice but no further improvement in C57BL/6J mice, and had no effect in DBA/2J mice. On testing the ability to extrapolate the direction of movement of a stimulus, administration of Noopept increased the proportion of correct responses in C57BL/6J and BALB/c mice, but had no effect in DBA/2J mice. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 57, No. 6, pp. 721–728, November–December, 2007.     

Quantitative and qualitative differences in bronchoalveolar inflammatory cells in Pseudomonas aeruginosa-resistant and -susceptible mice

The difference in severity of Pseudomonas aeruginosa-induced chronic lung infection may be determined by differences in host inflammatory responses. In the present study we investigate this possibility using BALB/c and C57Bl/6 mice, resistant and susceptible, respectively, to chronic lung infection with P. aeruginosa. Following intratracheal inoculation of P. aeruginosa-impregnated agar beads, C57Bl/6 mice mounted a stronger inflammatory response with significantly higher total cell numbers in the bronchoalveolar lavage fluid compared with BALB/c mice. While polymorphonuclear leucocytes were the predominant cell in C57Bl/6 mice, macrophages constituted the majority in BALB/c mice at day 7 post-infection. Alveolar macrophages from C57Bl/6 mice showed significantly higher spontaneous production of nitric oxide (NO) at day 7 post-infection compared with BALB/c mice. Following in vitro stimulation with heat-killed Pseudomonas antigen, these cells produced significantly higher NO compared with cells from BALB/c mice at day 21 post-infection. Production of tumour necrosis factor-alpha (TNF-α) by alveolar macrophages was significantly higher at day 7 in BALB/c mice compared with C57Bl/6 mice, which showed significantly higher levels at day 28 post-infection. Taken together, these results suggest that defects in the host inflammatory process contribute to the variable outcome of chronic lung infection with P. aeruginosa. An exaggerated inflammatory response dominated by polymorphonuclear cells correlates with susceptibility to infection, whilst a modest inflammatory response dominated by macrophages correlates with resistance. Moreover, the quantity and timing of production of NO and TNF-α by alveolar macrophages may modulate the course and outcome of infection.     

Spontaneous expression of endogenous type C RNA virus by BALB/c splenic B lymphocytes in continuous culture.

B-lymphocyte cultures were established from spleens of BALB/c, C57B1/6, NIH Swiss, and SWR mice of various age groups. Spontaneous, consistent, and thus predictable release of a B-tropic mouse endogenous virus occurred from the very first passage in cultured lymphocytes derived from BALB/c mice 6 months old or older but not from similar lymphocytes derived from BALB/c mice of 1.5 or 3 months of age. C57Bl/6, NIH Swiss, and SWR mice belonging to various age groups ranging between 1.5 and 18 months failed to exhibit such a spontaneous release of viral particles. We conclude that in BALB/c splenic B lymphocytes a breakdown of cellular control mechanisms occurs in older animals leading to viral production while such a phenomenon is absent in C57Bl/6, NIH Swiss, and SWR mice.     

Effects of Selank on behavioral reactions and activities of plasma enkephalin-degrading enzymes in mice with different phenotypes of emotional and stress reactions

Comparative study of plasma activities of enkephalin-degrading enzymes in mice with different phenotypes of emotional and stress reactions revealed significant differences between intact BALB/c and C57Bl/6 mice by the half-life of plasma leu-enkephalin. Selank in a dose of 100 /kg produced an anxiolytic effect in the open-field test and increased the half-life of plasma leu-enkephalin in BALB/c mice, but had no effect on behavioral reactions and enkephalinase activities in C57Bl/6 mice. Our results suggest that anxiolytic activity of Selank is associated with inhibition of enkephalin-degrading enzymes.     

BALB/c and C57Bl/6 mice infected with virulentBurkholderia pseudomalleiprovide contrasting animal models for the acute and chronic forms of human melioidosis

Burkholderia pseudomalleiis the aetiological agent of melioidosis, a life-threatening bacterial disease occurring in many species of animals, including man. Infection in humans commonly manifests as one of three clinical presentations: acute, subacute or chronic disease. Investigations were undertaken to assess the suitability of BALB/c and C57Bl/6 mice as animal models for the different forms of human melioidosis. The course of infection in BALB/c mice was similar to that which occurs in acute human infection. By contrast, infection of C57Bl/6 mice appeared to mimic chronic human melioidosis. While BALB/c mice suffered a rapidly-progressive bacteraemia which resulted in host death by 96 h, C57Bl/6 mice were able to prevent this, and typically remained asymptomatic for up to 6 weeks. LD₅₀values of 4 cells and 2.5×10⁴cells for BALB/c and C57Bl/6 mice, respectively, reflect these observations. The heightened level of resistance toB. pseudomalleiobserved in C57Bl/6 mice was suggested to have a genetic basis, when the susceptibilities of first filial and reciprocal backcross generations were examined. Growth kinetics ofB. pseudomalleiwithin BALB/c and C57Bl/6 peritoneal exudate cell (PEC) cultures were examined to investigate PEC microbicidal efficiency as a determinant of host susceptibility. C57Bl/6 PEC cultures exhibited greater microbicidal efficiency towardsB. pseudomalleiwhen compared to BALB/c cells, indicating that susceptibility may be determined by non-specific, cellular mechanisms. Collectively, these results suggest that the BALB/c and C57Bl/6 strains of mice may provide excellent models for acute and chronic human melioidosis, respectively.     

Experimental African trypanosomiasis: differences in cytokine and nitric oxide production by macrophages from resistant and susceptible mice.

Immunosuppression in experimental infections with Trypanosoma congolense is mediated by the synergistic action of macrophages and a novel lymphocyte(s), which involves the activity of IFN-gamma as well as IL-10. BALB/c mice are highly susceptible while C57Bl/6 mice are relatively resistant to T. congolense infections. Plasma and/or supernatants of spleen cell cultures of infected susceptible BALB/c mice have more IL-10 but less IL-12 than those of infected relatively resistant C57Bl/6 mice. Cells of a BALB/c macrophage cell line, when pulsed with T. congolense, produce more IL-10 and IL-6, but have less TNF-alpha mRNA, than equally treated cells of a C57Bl/6 cell line. Peritoneal and/or bone marrow-derived macrophages obtained from BALB/c mice, pulsed with T. congolense in culture, produce less nitric oxide, TNF-alpha and IL-12, but more IL-6 and IL-10 than equally treated macrophages isolated from C57Bl/6 mice. We suggest that genetic resistance to African trypanosomiasis is expressed at the level of the macrophage.     

Multidimensional assessment of differences in monoamine metabolism in C57Bl/6 and BALB/c mice

Monoamine metabolism in the hypothalamus and striatum of BALB/c and C57Bl/6 mice (intact and stressed in the open field test) was studied using single-and multidimensional statistical methods. It is suggested that the revealed difference in neurotransmitter metabolism is associated with genetically controlled behavior of these animals under conditions of emotional stress. The results of discriminant analysis suggest that the regulation of monoamine metabolism during emotional stress is genetically determined. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 5, pp. 574–577, May, 2000     

Growth of transplantable melanoma and leukaemia and prevention of virus-induced leukaemia in long lived radiation chimeras constructed with unmanipulated bone marrow.

Haemopoietic radiation chimeras across the H-2 barrier (BALB/c----C57Bl/6; H-2d----H-2b chimeras and vice versa) have been studied for their capacity to suppress the growth, or to reject, transplantable B16 melanotic melanoma and radiation leukaemia virus-induced, transplantable leukaemia. Also, radiation leukaemia virus (RadLV) obtained from the thymus of leukaemic C57Bl/6 mice was injected i.p. into established chimeras (H-2d----H-2b). As expected, long lived, graft versus host disease free allogeneic chimeras constructed with intact bone marrow were unable to reject the tumours both when recipients were BALB/c----C57Bl/6 or C57Bl/6----BALB/c chimeras. However, also inoculation of a large number of immunocompetent cells from normal BALB/c mice into BALB/c----C57Bl/6 chimeras, failed to promote a rejection of the tumours. On the contrary, the same amount of syngeneic (BALB/c) immunocompetent cells prevented growth of melanoma when transferred into athymic nude BALB/c mice, while the tumour grew unimpaired in untreated athymic nude BALB/c mice. The same type of H-2d----H-2b chimeras displayed complete resistance to inculation of leukaemogenic H-2b restricted RadLV while all H-2b----H-2b, syngeneically reconstituted mice developed disseminated leukaemia. These findings demonstrate that: (a) a powerful suppressive principle operates in the chimeras which does not allow effector function and anti-tumour activity of passively transferred normal, mature T cells from resistant BALB/c mice. Thus, no H-2 restriction of donor T cells can be advocated for suppression of anti-tumour effector functions in the chimeras. (b) New donor (BALB/c, H-2d) marrow character in the H-2d----H-2b chimeras prevents expression of the H-2b restricted viral activity and leukaemogenic transformation and/or proliferation.     

Differential effects of lorazepam on sleep and activity in C57BL/6J and BALB/cJ strain mice

Compared to C57BL/6 mice, BALB/c mice exhibit greater 'anxiousness' on behavioural tests of anxiety, and can show significantly longer sleep disruptions after exposure to anxiogenic situations. Relative to C57BL/6 mice, BALB/c mice also have reduced benzodiazepine (BZ) receptor densities in the brain and fivefold less BZ receptor density in the amygdala, a region important in anxiety and in the control of arousal. Lorazepam is a BZ receptor full agonist and has been used to treat both anxiety and insomnia. Differences between C57BL/6 and BALB/c mice raise the question of whether BZ agonists would impact sleep and activity differentially in the two strains. We examined the effects of two doses of lorazepam (0.5 and 1.5 mg kg⁻¹) or saline alone (0.2 mL) on sleep and activity in C57BL/6 ( n  =   8) and BALB/c ( n  =   7) mice. Compared to saline, both doses of lorazepam significantly increased non-rapid eye movement (NREM) and reduced activity in both strains. In C57BL/6 mice, rapid eye movement (REM) was increased at both doses. In BALB/c mice, the 0.5 mg kg⁻¹ dose had no significant influence on REM, whereas REM was reduced significantly after the 1.5 mg kg⁻¹ dose. The results demonstrate significant differences between C57BL/6 and BALB/c mice in the effects of lorazepam on REM, whereas the effects on NREM and activity were similar. Strain differences in the number of BZ receptors in the amygdala, but not other brain regions, suggests possible site specificity in the effects of lorazepam on REM. These differences in BZ-binding sites in the amygdala could be a significant factor in differences in the sleep response between C57 and BALB/c mice.