Is unpredictable chronic mild stress (UCMS) a reliable model to study depression-induced neuroinflammation?

Farooq, Rai Khalid; Isingrini, Elsa; Tanti, Arnaud; Guisquet, Anne-Marie Le; Arlicot, Nicolas; Minier, Frédéric; Leman, Samuel; Chalon, Sylvie; Belzung, Catherine; Camus, Vincent

doi:10.1016/j.bbr.2012.03.020

Cited by 145 publications

(98 citation statements)

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“…The total score per test was derived by summing the individual scores for each body part. 78,87,92 Immediately after scoring coat status, mice were exposed to the splash test 93,94 which involves spraying a 10% sucrose solution onto the dorsal coat of mouse in its home cage. This mildly sticky solution induces self-grooming the duration of which was recorded for 5 min by 2-3 observers blinded to mouse genotype.…”

Section: Unpredictable Chronic Mild Stress (Ucms)mentioning

confidence: 99%

Mice Genetically Depleted of Brain Serotonin Do Not Display a Depression-like Behavioral Phenotype

Angoa‐Pérez

Kane

Briggs

et al. 2014

ACS Chem. Neurosci.

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Reductions in function within the serotonin (5HT) neuronal system have long been proposed as etiological factors in depression. Serotonin selective reuptake inhibitors (SSRIs) are the most common treatment for depression and their therapeutic effect is generally attributed to their ability to increase the synaptic levels of 5HT. Tryptophan hydroxylase 2 (TPH2) is the initial and ratelimiting enzyme in the biosynthetic pathway of 5HT in the CNS and losses in its catalytic activity lead to reductions in 5HT production and release. The time differential between the onset of 5HT reuptake inhibition by SSRIs (minutes) and onset of their anti-depressant efficacy (weeks to months), when considered with their overall poor therapeutic effectiveness, has cast some doubt on the role of 5HT in depression. Mice lacking the gene for TPH2 are genetically depleted of brain 5HT and were tested for a depression-like behavioral phenotype using a battery of valid tests for affective-like disorders in animals. The behavior of TPH2 −/− mice on the sucrose preference test, tail suspension test and forced swim test and their responses in the unpredictable chronic mild stress and learned helplessness paradigms was the same as wild-type controls. While TPH2−/− mice as a group were not responsive to SSRIs, a subset responded to treatment with SSRIs in the same manner as wild-type controls with significant reductions in immobility time on the tail suspension test, indicative of antidepressant drug effects. The behavioral phenotype of the TPH2 −/− mouse questions the role of 5HT in depression. Furthermore, the TPH2 −/− mouse may Detroit, MI 48201-1916. Phone: 313-476-4457, Fax: 313-576-1112. donald.kuhn@wayne.edu. Author Contributions MAP, MJK, DIB, NHM and CES conducted the in vivo behavioral and pharmacological experiments. DMF and MAP conducted the in vitro synaptosomal 5HT uptake experiments. MAP, MJK and DMK interpreted the data. MAP, MJK and DMK conceived of project and wrote the paper. All authors edited and approved the final version of the manuscript. NotesThe authors declare no competing financial interest. SUPPORTING INFORMATION AVAILABLEThe numbers of TPH2+/+ and TPH2−/− mice classified as responders or non-responders (specified by sex) to the SSRIs fluoxetine, citalopram and paroxetine is included in SI Table 1. The immobility time cutoff values for defining whether a subject was classified as a responder or non-responder to SSRIs is presented in SI Table 2. Information on the specific stressors used in the UCMS is included in SI Table 3. This information is available free of charge via the Internet at http://pubs.acs.org. U.S. Department of Veterans Affairs VA Author ManuscriptVA Author Manuscript VA Author Manuscriptserve as a useful model in the search for new medications that have therapeutic targets for depression that are outside of the 5HT neuronal system. Keywordsserotonin; TPH2; TPH2 knock out; depression-like behavior; SSRIs; SERT The serotonin (5HT) neuronal system innervates nearly the entire neuraxis from...

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Section: Unpredictable Chronic Mild Stress (Ucms)mentioning

confidence: 99%

Mice Genetically Depleted of Brain Serotonin Do Not Display a Depression-like Behavioral Phenotype

Angoa‐Pérez

Kane

Briggs

et al. 2014

ACS Chem. Neurosci.

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“…The purpose of CUMS animal model is therefore to determine the relation between the behavioral changes caused by stressful situations which tested animals are subjected to, and the identification of the clinical symptoms of depression [5].…”

Section: Resultsmentioning

confidence: 99%

“…CUMS performed on rodents is often used to explain the pathophysiology of nerve inflammation in depression and to assess disorders associated with an increased risk of neurodegenerative diseases [5]. Clinical and pre-clinical data show that depression is associated with activation of the immune system, which is manifested as the inflammation state.…”

Section: Neuronal Processes and Brain Structures Involved In The Cumsmentioning

confidence: 99%

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Utility of the chronic unpredictable mild stress model in research on new antidepressants

Pekala

Budzyńska

Biała

2014

Current Issues in Pharmacy and Medical Sciences

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conducted in order to mimic the similarities of clinical symptoms of depression, in laboratory condition. These models make testing many factors involved in the pathogenesis, etiology, symptomatology, and the pharmacological treatment of depression possible [2].The incidence of depression and its negative consequences still have been intensely studied. The "ideal" animal model of depression should have as many criteria specific to depression in humans as possible, should be sensitive to antidepressants, and should identify similarities in the pathophysiology and etiology of different kind of depressive states [31]. It should be noted that animal models of depression do not always reflect all the irregularities of depression in humans. However, patients do not always reveal all possible symptoms of this disease, either. We may mention here anhedonia, one of the primary symptoms of depression in humans, whereas most of the current animal models of depression only mimic it [9]. MODELS OF DEPRESSIONCurrently, many various models of depression have been used to mimic depressive state in humans. Each model has advantages and disadvantages. The most commonly used paradigms are as follows:Learned helplessness. In this paradigm the depressive state is induced by uncontrolled and unpredictable electric shock in rodents. Model of learned helplessness was firstly used at the early 60's. In these experiments, animals are Unpredictable chronic mild stress model was developed as an animal model of depression more than 20 years ago. Essential for this model is that after prolonged exposure of tested animals to a series of unpredictable mild stressors, a condition similar to anhedonia develops, which is observed in the majority of depressive disorders. Unpredictable chronic mild stress model is used nowadays in numerous studies related to the neurobiological and biochemical changes associated with depressive illness. Their results confirm that chronic unpredictable mild stress induces in tested animals a number of changes, which reflect those seen in depressive disorders. Because the effects of unpredictable chronic mild stress can be used in a more accurate diagnosis of the pathophysiology of depressive illness and expand knowledge of its pharmacotherapy, therefore research in this area has been continued all the time.

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“…A recent study of a sample of patients with first onset psychosis reported that increased IL-6 expression and higher salivary cortisol levels predicted smaller hippocampal volumes and that a history of childhood maltreatment was related to current inflammatory markers 79 . It is suggested that IL-6 inhibits adult neurogenesis by stimulating the Hypothalamic-Pituitary-Adrenal (HPA) axis 80 and by acting on the IL-6 receptor or a common signal transducer, glycoprotein 130 (gp130), in the dentate gyrus 81 .…”

Section: Neuroinflammation and Neurogenesismentioning

confidence: 99%

Neuroinflammation in Schizophrenia Focused on the Pharmacological and Therapeutic Evidence

Xu¹

2015

Pharmacologia

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Background: Schizophrenia is a heterogeneous mental disorder with a variety of symptoms. Although, there are no pathognomonic abnormalities in brains of schizophrenia patients, recent years have witnessed research progresses in revealing pathologic changes in cellular and molecular levels. Objective: This article reviewed recent human studies showing neuroimmune alterations in schizophrenia patients and offered explanations for roles of neuroinflammation in the pathogenesis of schizophrenia by citing some of experimental data from non-human studies. The focus of this review was put on pharmacological and therapeutic evidence pointing to a recommendation of anti-inflammatory treatment for patients with schizophrenia. Particularly, it provided compelling evidence supporting an anti-inflammatory effect of antipsychotics by reviewing a relatively large body of studies in the categories of in vitro, animals and humans. Conclusion: Then, it reviewed recent clinical trials with minocycline, a second-generation tetracycline, or the selective COX-2 inhibitor celecoxib. Most of these clinical trials provided promising results of superior beneficial treatment effects as the consequence of co-administration of standard antipsychotic drugs and anti-inflammatory compounds, compared with antipsychotic drugs alone.

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Is unpredictable chronic mild stress (UCMS) a reliable model to study depression-induced neuroinflammation?

Cited by 145 publications

References 51 publications

Mice Genetically Depleted of Brain Serotonin Do Not Display a Depression-like Behavioral Phenotype

Mice Genetically Depleted of Brain Serotonin Do Not Display a Depression-like Behavioral Phenotype

Utility of the chronic unpredictable mild stress model in research on new antidepressants

Neuroinflammation in Schizophrenia Focused on the Pharmacological and Therapeutic Evidence

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