Wyniki wyszukiwania - Biblioteka Nauki

1

Czy mozna miec wiecej niz dwoje rodzicow ?

100%

Basta-Kaim A.

Wszechświat

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1992

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tom 93

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nr 02

31-33

2

Effect of co-treatment with fluoxetine and amantadine on the behavioral and immunological parameters of rats subjected to the forced swimming test

67%

Roguz Z. , Kubera M. , Basta-Kaim A.

Acta Neurobiologiae Experimentalis

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2009

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tom 69

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nr 3

EN

Considerable attention has been paid to a possible role of immunological dysregulation in the pathogenesis of depression. It has been reported that combined administration of antidepressant drugs and the non-competitive NMDA receptor antagonist amantadine (AMA) reduces immobility time in the forced swimming test. Moreover, preliminary clinical data show that such a combination of drugs has benefi cial effects in treatment-resistant depressed patients. Since immune activation and a pro-infl ammatory response are clearly evident in treatment-resistant depression, the aim of the present study was to examine the effect of an antidepressant combination of FLU and AMA on immune parameters in rats subjected to the forced swimming test. The obtained results revealed synergistic antidepressant effects of combined administration of FLU (10 mg/kg) and AMA (10 mg/kg) – drugs otherwise ineffective when given separately in such doses. The antidepressant activity was accompanied with a reversal of the stress-induced increase in the proliferation of splenocytes in response to concanavalin A, and a signifi cant enhancement in the production of the negative immunoregulator interleukine-10. Moreover, the relative spleen weight in these rats was also reduced after joint administration of FLU with AMA in comparison with rats treated with the vehicle. In summary, the antidepressive effi cacy of a combination of FLU and AMA given in suboptimal doses may be related to their negative immune effects.

3

The effect of antidepressant drugs on immunoendocrine changes in animal models of depression

51%

Budziszewska B. , Kubera M. , Szymanska M. , Basta-Kaim A. , Grygier B. , Lason W.

Acta Neurobiologiae Experimentalis

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2009

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tom 69

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nr 3

EN

Exacerbated glucocorticoids and cytokines action are essential factor in the pathogenesis of depression, and the effects of antidepressant drugs on these parameters are poorly recognized.We investigated the effect of antidepressant drugs on the HPA axis activity in prenatally stressed S-D rats and on cell-mediated immunity in Wistar rats and C57BL/6 mice subjected to chronic mild stress (CMS) model of depression. The activity of HPA axis was estimated by measuring the level of glucocorticoid receptors (GR) and activity of some kinases which are known to infl uence GR action. Adult rats subjected to prenatal stress displayed prolonged immobility in the Porsolt test and in open-fi eld test, elevated corticosterone level, increased GR level in the hippocampus but not in frontal cortex. They also showed decreased FKBP51 in the frontal cortex, but not in hippocampus, decreased the active, phosphorylated form of the JNK1 and 2 kinase in the hippocampus and the active form of p38-MAPK in the frontal cortex. Chronic imipramine, fl uoxetine, mirtazapine or tianeptine administration normalized most of these parameters. In CMS model of depression anti-anhedonic effect of imipramine was accompanied by decreased proliferative activity of splenocytes and their ability to produce pro-infl ammatory cytokines in rats. In desipramine treated mice subjected to CMS increased ability of T cells to produce negative immunoregulator IL-10 and decreased the cytotoxic activity of NK cells were observed.

4

Inhibitory effect of neurosteroids on gluicocorticoid receptor-mediated gene transcription:an involvement of protein kinases and interaction with psychotropie drugs

51%

Leskiewicz M. , Basta-Kaim A. , Budziszewska B. , Tetich M. , Otczyk M. , Lason W.

Acta Neurobiologiae Experimentalis

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2005

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tom 65

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nr 3

5

Brain level of FKBP-51, a glucocorticoid receptor cochaperone, is decreased in a neurodevelopmental animal model of schzophrenia

51%

Basta-Kaim A. , Budziszewska B. , Kabera M. , Leskiewicz M. , Regulska M. , Korzeniak B.

Acta Neurobiologiae Experimentalis

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2009

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tom 69

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nr 3

EN

Recent studies suggest that dysregulation of the HPA axis activity and disturbance in glucocorticoid receptor (GR) action are involved in the pathogenesis of schizophrenia. The hyperfunction of GR can result from alterations in GR phosphorylation status or numbers of its cochaperones. The most important GR cochaperone FKBP-51, is known to inhibit GR transcriptional activity. The aim of the present work was to investigate the concentration of the immunophilin FKBP-51 in the hippocampus and frontal cortex in a neurodevelopmental animal model of schizophrenia. This model is based on administration of lipopolysaccharide to pregnant rats (in the second and third week of pregnancy). Amount of FKBP-51 was measured by Western blot method. In order to verify the above model, exploration, effi cacy of sensorimotor gating and performance in the social interaction test were determined. Prenatal LPS treatment induced behavioral disturbances typical of schizophrenia, like sensorimotor gating defi cit, higher exploratory activity and changes in social interaction test in the adult offspring. Furthermore, the level of the immunophilin FKBP51 was lower in both female and male offspring. These results suggest that multiple administrations of LPS to pregnant rats evoke GR hyperfunction in adult offspring by decreasing the concentration of FKBP-51, a protein which is known to inhibit GR function. This study was partially supported by the grant N40101231/0174 from the MSHE, Warsaw, Poland.

6

Effects of neurosteroids on neuronal survival: Molecular basis and clinical perspectives

51%

Leskiewicz M. , Budziszewska B. , Basta-Kaim A. , Zajac A. , Kacinski M. , Lason W.

Acta Neurobiologiae Experimentalis

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2006

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tom 66

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nr 4

EN

Neurosteroids have long been known to act as important modulators of central nervous system functions. The concept of their mechanism of action, however, have essentially undergone an evolution. Previously, these compounds were postulated to regulate neuronal function mainly via allosteric regulation of some membrane-bound receptors, such as GABAA and NMDA receptors, in a non-genomic way. Recent studies have provided evidence for intracellular targets for neurosteroids, e.g., transcription factors (NFk-B, progesterone receptors), protein kinases (phosphatidylinositol 3-kinase, protein kinase C), or microtubule-associated proteins, i.e. factors essential in regulation of neuronal survival and apoptosis. This paper reviews in vitro and in vivo data on neurosteroid involvement in the regulation of neurodegenerative processes with emphasis on new intracellular and genomic mechanisms of their action. Potential utility of neurosteroids in the treatment of some neurodegenerative disorders has been also discussed.

7

Inhibitory effect of antipsychotic drugs on the CON A- and LPS- induced proliferative activity of mouse splenocytes: a possible mechanism of action

51%

Basta-Kaim A. , Budziszewska B. , Jagla G. , Nowak W. , Kubera M. , Lason W.

Journal of Physiology and Pharmacology

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2006

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tom 57

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nr 2

EN

Antipsychotic drugs are widely used to alleviate a number of psychic disorders and have been found to modulate some immune parameters, but the molecular mechanism of their action on the proliferative activity has been poorly recognized. In the present study, we investigated effects of various antipsychotics on the proliferative activity of lymphocytes stimulated by concanavalin A (Con A) and lipopolysaccharide (LPS). Chlorpromazine (3x10-6 - 10-4M) showed the most potent effect in inhibiting 3H-thymidine incorporation into C57BL/6 mouse spleen cells stimulated by Con A and LPS. Treatment of the cells with thioridazine (10-5 - 10-4M), promazine (10-5 - 10-4M), haloperidol (10-5 - 10-4M), risperidone (10-5 - 10-4M), raclopride (3x10-5 - 10-4M), remoxipride (3x10-5 - 10-4M) and clozapine ( 3x10-5 - 10-4M), but not with sulpiride (10-7 - 10-4M), suppressed proliferative activity of splenocytes after Con A stimulation. On the other hand, LPS-induced proliferation of splenocytes was inhibited by clozapine, promazine, thioridazine and haloperidol, but not by risperidone, remoxipride, sulpiride and raclopride. In the next part of the study, the influence of some kinase modulators on chlorpromazine- and clozapine-evoked inhibition of the proliferative activity of splenocytes was determined. Wortmannin, a selective phosphatidylinositol 3-kinase (PI3-K) inhibitor, blocked chlorpromazine and clozapine inhibitory effect on the mitogen-stimulated splenocyte proliferation. The involvement of PI 3-K /protein kinase B (PKB, Akt) pathway was confirmed by the results of the Western blot study, which showed that both drugs increased the level of active phospho-Ser-473 Akt, without changing the total Akt level, and decreased the level of active, nonphosphorylated glycogen synthase kinase-3 (GSK-3ß). Additionally, we have found that chlorpromazine action was also attenuated by a selective p-38-MAPK inhibitor, while clozapine effect was suppressed by a protein kinase C (PKC) activator. The obtained results indicated that atypical antipsychotic drugs markedly inhibited the proliferative activity of splenocytes only after ConA stimulation. Inhibition of the proliferative capability of splenocytes by chlorpromazine and clozapine resulted mainly from the activation of PI3-K/Akt pathway.

8

Effects of combined treatment with imipramine and metyrapone on the immobility time, the activity of hypothalamo-pituitary-adrenocortical axis and immunological parameters in the forced swimming test in the rat

51%

Rogoz Z. , Budziszewska B. , Kubera M. , Basta-Kaim A. , Jaworska-Feil L. , Skuza G. , Lason W.

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nr 1

EN

Major depression is frequently associated with the hyperactivity of the hypothalamic-pituitary-adrenocortical axis, and glucocorticoid synthesis inhibitors have been shown to exert antidepressant action. The aim of the present study was to examine the effect of joint administration of metyrapone (50 mg/kg) and imipramine (5 and/or 10 mg/kg) on immobility time, plasma corticosterone concentration, the weight of spleens and thymuses and the proliferative activity of splenocytes in rats subjected to the forced swimming test - an animal model of depression. Metyrapone alone (50 mg/kg) reduced the immobility time of rats in the forced swimming test and decreased plasma corticosterone level, but did not change immunological parameters. Joint administration of metyrapone and imipramine (5 and 10 mg/kg) produced a more pronounced antidepressant-like effect than either of the drugs given alone. The forced swimming procedure significantly increased the proliferative activity of splenocytes, that parameter being reduced only by co-administration of metyrapone and imipramine. Joint administration of metyrapone and imipramine inhibited to a similar extend the corticosterone level as did treatment with metyrapone alone (about twofold); however, the plasma corticosterone level in animals treated with metyrapone and the higher dose of imipramine did not differ from the concentration of this steroid in control, not-stressed rats. The obtained results indicate that metyrapone potentiates the antidepressant-like activity of imipramine and exerts a beneficial effect on the stress-induced increase in plasma corticosterone concentration and the proliferative activity of splenocytes. These finding suggest that a combination of metyrapone and an antidepressant drug may be useful for the treatment drug-resistant depression and/or depression associated with a high cortisol level.

9

Immunomodulatory effect of antidepressant drugs in animal models of depression

43%

Kubera M. , Basta-Kaim A. , Budziszewska B. , Jaworska-Feil E. , Roman A. , Leskiewicz M. , Telich M. , Korzeniak B. , Lason W.

Acta Neurobiologiae Experimentalis

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2005

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tom 65

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nr 3

10

The decrease in JNK- and p38-MAP kinase activity is accompanied by the enhancement of PP2A phosphatase level in the brain of prenatally stressed rats

43%

Budziszewska B. , Szymanska M. , Leskiewicz M. , Basta-Kaim A. , Jaworska-Feil L. , Kubera M. , Jantas D. , Lason W.

Journal of Physiology and Pharmacology

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2010

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tom 61

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nr 2

EN

Our previous study suggests that in prenatal stress model of depression glucocorticoid receptor (GR) function in adult rats is enhanced. However, the long-term consequences of stress, a causal factor in depression, on intracellular elements involved into the regulation of GR function is poorly examined. Mitogen-activated protein kinases (MAPKs), activity of which is disturbed in depression, are important regulators of GR action, so they can mediate the effect of stress on GR function. Therefore, the aim of the present study was to investigate the levels of active phosphorylated forms of extracellular signal-regulated kinases (ERK), Jun N-terminal kinases (JNK) and the p38 kinase in the hippocampus and frontal cortex in rats subjected to prenatal stress. The concentration of MAP kinase phosphatase (MKP-1, MKP-2) and protein phosphatase-2A (PP2A), which dephosphorylate all forms of MAP kinases, were also determined. During verification of the applied model of depression, we found that prenatally stressed rats displayed high level of immobility in the Porsolt test and that the administration of imipramine, fluoxetine, mirtazapine and tianeptine for 21 days normalized this parameter. Western blot study revealed that rats subjected to prenatal stress had decreased levels of p-JNK1 and p-JNK2 in the hippocampus and p-p38 in the frontal cortex, but the concentrations of p-ERK1 and p-ERK2 were not changed. Chronic treatment with imipramine inhibited the stress-induced decrease in p-JNK1/2, while imipramine, fluoxetine and mirtazapine blocked changes in p-p38. PP2A phosphatase level was higher in the hippocampus and frontal cortex in prenatally stressed animals than in control rats. Chronic treatment with antidepressant drugs attenuated the stress-induced increase in the level of this phosphatase, but had no effect on its concentration in control animals. There was no significant difference in MKP-1 and in MKP-2 levels in both brain structures between control and prenatally stressed rats. The obtained results showed that prenatal stress decreased the levels of active form of JNK and p38, but enhanced PP2A phosphatase expression and most of these changes were reversed by antidepressant drugs. Since p-JNK and p-p38 are known to inhibit GR function their lowered levels may enhance glucocorticoid action. Furthermore, the increased PP2A concentration may intensify GR action not only by inhibition of JNK and p38 phosphorylation, but also by a direct influence on the process of GR translocation.

11

The effect of amphetamine sensitization on mouse immunoreactivity

43%

Kubera M. , Filip M. , Basta-Kaim A. , Nowak E. , Budziszewska B. , Tetich M. , Holan V. , Korzeniak B. , Przegalinski E.

Journal of Physiology and Pharmacology

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2002

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tom 53

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nr 2

EN

Recent studies indicate a role of the immune system in the behavioral effects of amphetamine in rodents. In the present study we attempted to find a connection between the behavioral changes induced by repeated, intermittent administration of amphetamine and some immunological consequences of sensitization to amphetamine in mice. Male Albino Swiss mice were treated repeatedly (for 5 days) with amphetamine (1 mg/kg, i.p.). On day 9, they received a challenge dose of amphetamine (1 mg/kg). Acute administration of amphetamine increased their locomotor activity by ca. 40%. In animals treated repeatedly with amphetamine, the challenge dose of the psychostimulant induced behavioral sensitization, i.e. the higher locomotor activation as compared with that after its first administration to mice. Immune functions were evaluated by the ability of splenocytes to proliferate and to produce cytokines such as interferongamma(IFN-gamma ), interleukin (IL)-4 and IL-10. Acute amphetamine administration significantly decreased, by ca. 30% and 25%, the proliferation of splenocytes in response to an optimal and a suboptimal dose of concanavalin A (Con A), respectively, and increased their ability to produce IL-4. Chronic intermittent treatment with amphetamine significantly decreased, by ca. 65% and 50%, the proliferative response of T cells to an optimal and a suboptimal dose of Con A, respectively, and diminished by 20% the metabolic activity of splenocytes. The above data showed that both acute and chronic amphetamine administration diminished some aspects of the cell-mediated immunity; nevertheless, immunosuppression was particularly evident in amphetamine-sensitized mice. Our findings seem to indicate possible importance of monitoring and correcting immune changes in the therapy of amphetamine addiction.

12

Effect of some antidepressants on the low corticosterone concentration-induced gene transcription in LMCAT fibroblast cells

43%

Otczyk M. , Mulik K. , Budziszewska B. , Jaworska-Feil L. , Basta-Kaim A. , Kubera M. , Jagla G. , Nowak W. , Lason W.

Journal of Physiology and Pharmacology

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2008

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tom 59

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nr 1

EN

The aim of the present study was to investigate effects of some classical and new antidepressants on functional activity of the glucocorticoid receceptor (GR) induced by low corticosterone concentration in mouse fibroblast cells stably transfected with mouse mammary tumor virus-chloramphenicol acetyltransferase plasmid (LMCAT cells). We found that the transcriptional activity of GR stimulated by 50 nM corticosterone was strongly attenuated by imipramine, desipramine, fluoxetine and tianeptine in a concentration-dependent way, whereas reboxetine had only a weak effect and venlafaxine was inactive. Further study revealed that the inhibitor of c-Jun N-terminal kinase - mitogen-activated protein kinase (JNK-MAPK), SP600125 (0.1 µM), reversed the imipramine-induced suppression of GR function, whereas the inhibitor of extracellular signal-regulated kinase (ERK)-MAPK, PD 98059 (15µM), potentiated the antidepressant action. No effect of selective inhibitors of p38-MAPK, phosphatidylinositol 3-kinase (PI3-K)/Akt, and glycogen synthase kinase (GSK-3) on the imipramine-induced inhibition of GR function was detected. These data indicate that the functional activity of GR evoked by low corticosterone concentration in LMCAT cells is efficiently inhibited by tricyclic antidepressants. Moreover, it was found that JNK- and ERK-MAPK were oppositely involved in the regulation of the imipramine-induced inhibition of the GR functional activity. Thus, the present study supports the notion that the interaction of antidepressants with GR may play a role in attenuating pathological hyperactivity of HPA axis in depression.

13

Brain spingolipids in hyperglycemia

34%

Car H. , Fiedorowicz A. , Prokopiuk S. , Bienias K. , Zendzian-Piotrowska M. , Chabowski A. , Kosacka I. , Tidhar R. , Futerman A. H. , Glombik K. , Basta-Kaim A.

Acta Neurobiologiae Experimentalis

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2015

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tom 75

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nr Supl.

EN

Ceramide (Cer) and sphingomyelin (SM) are members of sphingolipid (SL) family. Their concentrationsin the brain undergo substantial changes in many pathologies. They are also important players in diabetes-linked brain dysfunctions, in which increased content of ceramides can be toxic to neurons. The aim of the study was to evaluate selected parameters of sphingolipids and insulin pathways in prefrontal cortex (PC) and hippocampus (H) of rats with experimentally induced hyperglycemia. STZ-rat model of type 1 diabetes and high fat diet model of insulin resistance were used. Analyses of studied parameters were performed by GLC, IHC and Elisa. We found the augmented levels of ceramides in H and PC and only minor in striatum and cerebellum of rats with STZ-induced diabetes. Similar expressions of Cer were confirmed by IHC. Myriocin, an inhibitor of an enzyme of ceramide de novo synthesis pathway, reduced ceramide generation in hyperglycemic brains, particularly in PC, which was reflected in altered Cer synthase activities. In addition, we reported the fluctuations in sphingomyelin levels in investigated structures. The level of insulin did not change in H and PC of STZ-treated rats. An expression of insulin receptor and its phosphorylated form decreased in both structures, but was restored after myriocin administration. Similarly, Akt and phosphorylated Akt changed in these structures suggesting important role of de novo Cer synthesis in intracellular pathways of insulin. In the rat model of high fat diet, which leads to insulin resistance, the sphingolipid pattern (Cer and SM) was altered in H and PC as well. Metformin, the drug of choice in diabetes type 2, influenced the content of the above SLs in these structures, suggesting the additional central activity of antidiabetic treatment. We conclude that ceramide and SM may be important mediators of diabetes- accompanied brain dysfunction.

14

The effect of antidepressant drugs on delayed-type hypersensitivity reaction in beta2M-/-, TCRdelta-/- and CD1d mice

34%

Kabera M. , Szczepanik M. , Majewska M. , Zemelka M. , Leskiewicz M. , Basta-Kaim A. , Budziszewska B. , Grygiel B. , Regulska M. , Korzeniak B. , Jagla G. , Nowak W. , Lason W.

Acta Neurobiologiae Experimentalis

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2009

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tom 69

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nr 3

EN

Delayed-type hypersensitivity (DTH) is a T cell-mediated immune reaction that plays a major role in the pathogenesis of various infl ammatory disorders. One of the most characteristic DTH phenomena is contact hypersensitivity (CS) used to assess cellmediated immunity against tumor cells and microbes that survive within macrophages. Recently it was suggested that activation of immune system plays a role in etiology of depression and that antidepressive agents have negative immunoregulatory effects. Our present studies showed that chronic fl uoxetine and desipramine administration signifi cantly inhibited CS reaction to picryl chloride (PCL) in B10.PLwild type mice (by 58% and 48%, respectively, when compared to positive control) and their inhibitory effect was even stronger in TCRd knockout mice. On the other hand in b2m-/- and CD1d-/- mice the prolonged antidepressant administration did not affect CS reaction. PCL sensitization signifi cantly increased spleen weight and proliferative activity of splenocytes in B10PL, TCRd-/- and b2m-/- mice. Prolonged antidepressant treatment attenuated this effect but only in B10PL mice. Presented data might suggest that inhibitory effect of desipramine and fl uoxetine on CS reaction could be caused by their infl uence on CD8+ and NKT regulatory cells that attenuate T cell-mediated immune response.

15

Prophylactic use of desupramine in wistar rats with high stress-sensitivity increases resistance to experimental tumor metastasis

34%

Kubera M. , Grygier B. , Lewandowska D. , Gruca P. , Rogoz Z. , Budziszewska B. , Basta-Kaim A. , Leskiewicz M. , Korzeniak B. , Jagla G. , Nowak W. , Lason W.

Acta Neurobiologiae Experimentalis

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2009

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tom 69

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nr 3

EN

The effect of antidepressant drugs on tumour progress in animals models of stress is very poorly recognized. Further more a role of susceptibility to stress in modulatory effect of antidepressant drug on tumour growth have not been studied. The aim of present study was to establish the effect of individual reactivity to stress and prophylactic two weeks desipramine administration on metastatic colonization of MADB 106 cells in lungs of Wistar rats. Rats were subjected by three weeks to chronic mild stress (CMS) model of depression and high-reactive and non-reactive rats were selected. Three months after CMS termination high-reactive and non-reactive animals were further subdivided: for two additional weeks the rats received daily injection of desipramine or saline. Tumor cells were injected two hours after last desipramine or saline administration. In stress-reactive, vehicle treated rats increase of number of lung metastasis in comparison to stress non-reactive, vehicle treated rats were observed. On the other hand chronic desipramine pretreatment signifi cantly increased survival rate and diminished number of lung metastasis in stress-sensitive animals although did not show such effect in stressresistant animals. Increase in rate of animal survival and decrease in lung metastasis can be connected with stimulatory effect of chronic desipramine pretreatment on NK cell activity. This study was supported by grant N40109732/2074 from Poland’s MS and HE.