Effects of fluoxetine, tianeptine and olanzapine on unpredictable chronic mild stress-induced depression-like behavior in mice

Mutlu, Oğuz; Gümüşlü, Esen; Ulak, Güner; Çelikyurt, İpek Komşuoğlu; Köktürk, Sibel; Kır, Hale Maral; Akar, Füruzan; Erden, Faruk

doi:10.1016/j.lfs.2012.09.023

Cited by 80 publications

(40 citation statements)

References 61 publications

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“…However, changing in grooming behaviour in the ST was seen only in UCMS-exposed male mice. Our study showed similarities [15,[29][30][31] and discrepancies [32][33] with earlier studies evaluating the physical and behavioural effects of UCMS. Discrepancies may be attributed to differential strain and sex susceptibility to UCMS, to variable protocols implemented in different laboratories, to differences of environmental conditions and to experimenter bias.…”

Section: Discussionsupporting

confidence: 72%

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Dipyrone ameliorates behavioural changes induced by unpredictable chronic mild stress: gender differences

Kıroğlu¹,

Demirkol²,

Berktaş³

et al. 2016

CIM

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Dipyrone ameliorates behavioural changes induced by unpredictable chronic mild stress: gender differences Abstract Purpose: Antidepressant effects of analgesics have been investigate in both clinical and experimental studies. The purpose of this study was to investigate if the analgesic-antipyretic drug, dipyrone, also had antidepressant-like effects.Methods: Depression-like effects were investigated in an unpredictable chronic mild stress (UCMS) model in both male and female mice. Cage changes, light-dark cycle reversal, cage tilting, wet floor, empty cage, foreign material on the floor and predator sounds were used to induce light stress at different times for six weeks. Dipyrone was administered intraperitoneally beginning from the third week. Splash, rota-rod (RR) and forced swimming (FST) tests were performed at the seventh week as behavioural tests to evaluate the antidepressant-like effects of dipyrone. Coat state score (CSS) and weights of animals were recorded at seventh weeks. Results were analyzed using one or two-way ANOVA followed by the Bonferonni post hoc test.Results: Weight of UCMS-exposed mice did not change compared with controls; however, significant changes were observed in CSS in both sexes of stressed mice (p<0.05). RR latency decreased and immobility time enhanced in FST test in both sexes of stressed mice (p<0.05). Grooming behaviour was not different between the groups in female mice, but different in male mice in the splash test. Dipyrone did not produce a significant change in CSS in the UCMS-exposed group but reversed the latency time and immobility time to normal values in both sexes of mice and augmented the number of grooming behaviour only in stressed male mice. Conclusion:These results indicate that dipyrone produce antidepressant-like effects to some symptoms of UCMS according to gender.SUPPLEMENT

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Section: Discussionsupporting

confidence: 72%

“…Except social stress, mice were exposed to the stressors in their own cage. To prevent habituation and provide an unpredictable feature, all stressors and/or sequences were administered at different time points every week [14,15].…”

Section: Experimental Groups and Drug Administrationmentioning

confidence: 99%

Dipyrone ameliorates behavioural changes induced by unpredictable chronic mild stress: gender differences

Kıroğlu¹,

Demirkol²,

Berktaş³

et al. 2016

CIM

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“…Indeed, the literature describing the effects of standard antidepressants on systemic inflammation is highly mixed. Although some studies have demonstrated that antidepressants decrease inflammatory cytokines (38,39), others report either no effect (31,40,41) or even increased levels (42,43). This discrepancy is likely due to a number of factors, including the class of antidepressant used for treatment or the heterogeneity of the patient population (44).…”

Section: Significancementioning

confidence: 99%

Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress

Hodes

Pfau

Leboeuf

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

570

506

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Significance Depression and anxiety have been linked to increased inflammation. However, we do not know if inflammatory status predates onset of disease or whether it contributes to depression symptomatology. We report preexisting individual differences in the peripheral immune system that predict and promote stress susceptibility. Replacing a stress-naive animal’s peripheral immune system with that of a stressed animal increases susceptibility to social stress including repeated social defeat stress (RSDS) and witness defeat (a purely emotional form of social stress). Depleting the cytokine IL-6 from the whole body or just from leukocytes promotes resilience, as does sequestering IL-6 outside of the brain. These studies demonstrate that the emotional response to stress can be generated or blocked in the periphery, and offer a potential new form of treatment for stress disorders.

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“…Prolonged activation of these systems by chronic stress results in persistently elevated cortisol levels that, in turn, can lead to maladaptive consequences in the organism and may ultimately contribute to the development of psychiatric disorders such as depression (de Kloet et al, 2005;McEwen, 2004). Animal models of chronic stress exposure are a valuable tool to further our understanding of the molecular underpinnings of stress-induced psychopathology (Savignac et al, 2011;Cryan and Holmes, 2005;Joëls and Baram, 2009), as well as providing a paradigm to assess and validate current and novel treatment strategies for depression Mutlu et al, 2012;Scharf et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Homer1/mGluR5 Activity Moderates Vulnerability to Chronic Social Stress

Wagner

Hartmann

Labermaier

et al. 2014

Neuropsychopharmacol

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Stress-induced psychiatric disorders, such as depression, have recently been linked to changes in glutamate transmission in the central nervous system. Glutamate signaling is mediated by a range of receptors, including metabotropic glutamate receptors (mGluRs). In particular, mGluR subtype 5 (mGluR5) is highly implicated in stress-induced psychopathology. The major scaffold protein Homer1 critically interacts with mGluR5 and has also been linked to several psychopathologies. Yet, the specific role of Homer1 in this context remains poorly understood. We used chronic social defeat stress as an established animal model of depression and investigated changes in transcription of Homer1a and Homer1b/c isoforms and functional coupling of Homer1 to mGluR5. Next, we investigated the consequences of Homer1 deletion, overexpression of Homer1a, and chronic administration of the mGluR5 inverse agonist CTEP (2-chloro-4-((2,5-dimethyl-1-(4-(trifluoromethoxy)phenyl)-1H-imidazol-4-yl)ethynyl)pyridine) on the effects of chronic stress. In mice exposed to chronic stress, Homer1b/c, but not Homer1a, mRNA was upregulated and, accordingly, Homer1/mGluR5 coupling was disrupted. We found a marked hyperactivity behavior as well as a dysregulated hypothalamic-pituitary-adrenal axis activity in chronically stressed Homer1 knockout (KO) mice. Chronic administration of the selective and orally bioavailable mGluR5 inverse agonist, CTEP, was able to recover behavioral alterations induced by chronic stress, whereas overexpression of Homer1a in the hippocampus led to an increased vulnerability to chronic stress, reflected in an increased physiological response to stress as well as enhanced depression-like behavior. Overall, our results implicate the glutamatergic system in the emergence of stress-induced psychiatric disorders, and support the Homer1/mGluR5 complex as a target for the development of novel antidepressant agents.

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Effects of fluoxetine, tianeptine and olanzapine on unpredictable chronic mild stress-induced depression-like behavior in mice

Cited by 80 publications

References 61 publications

Dipyrone ameliorates behavioural changes induced by unpredictable chronic mild stress: gender differences

Dipyrone ameliorates behavioural changes induced by unpredictable chronic mild stress: gender differences

Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress

Homer1/mGluR5 Activity Moderates Vulnerability to Chronic Social Stress

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