The effect of unpredictable chronic mild stress on depressive-like behavior and on hippocampal A1 and striatal A2A adenosine receptors

Crema, Leonardo Machado; Pettenuzzo, Letícia Ferreira; Schlabitz, Michele; Diehl, Luisa Amalia; Hoppe, Juliana Bender; Mestriner, Régis Gemerasca; Laureano, Daniela Pereira; Salbego, Christianne Gazzana; Dalmaz, Carla; Vendite, Deusa

doi:10.1016/j.physbeh.2012.11.001

Cited by 44 publications

(31 citation statements)

References 57 publications

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“…The neuroprotective effects of adenosine may prevent a possible neurotoxicicty induced by stress, specially associated to activation of adenosine A 1 receptors [67]. Crema and colleagues [41] showed that rats subjected to unpredictable chronic mild stress increased A 1 adenosine receptor binding and immunoreactivity in hippocampus, as well as increased striatal A 2A adenosine receptor binding in the striatum, whereas chronic restraint stress presented only an increase in A 1 adenosine receptor binding. There are several differences in the experimental setup and results between the chronic stress models in rodents and the model evaluated in our study using zebrafish.…”

Section: Discussionmentioning

confidence: 99%

“…There are two different enzymes with ADA activity, named ADA1 and ADA2; however, another protein with high similarity to the typical ADA was identified in zebrafish and is named adenosine deaminase-like (ADAL) [40]. Evidence demonstrated that adenosine receptors may be altered during chronic stress [41,42], and changes in the concentrations of extracellular ATP [43] and adenosine in rodents [44] have also been observed after exposure to stressors. Studies have already demonstrated that acute restraint stress altered ADA activities in zebrafish brain [18].…”

Section: Introductionmentioning

confidence: 99%

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Unpredictable Chronic Stress Alters Adenosine Metabolism in Zebrafish Brain

et al. 2015

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Stress is considered a risk factor for several human disorders. Despite the broad knowledge of stress responses in mammals, data on the relationship between unpredictable chronic stress (UCS) and its effects on purinergic signaling are limited. ATP hydrolysis by ectonucleotidases is an important source of adenosine, and adenosine deaminase (ADA) contributes to the control of the nucleoside concentrations. Considering that some stress models could affect signaling systems, the objective of this study was to investigate whether UCS alters ectonucleotidase and ADA pathway in zebrafish brain. Additionally, we analyzed ATP metabolism as well as ada1, ada2.1, ada2.2, adaL, and adaasi gene expression in zebrafish brain. Our results have demonstrated that UCS did not alter ectonucleotidase and soluble ADA activities. However, ecto-ADA activity was significantly decreased (26.8%) in brain membranes of animals exposed to UCS when compared to the control group. Quantitative reverse transcription PCR (RT-PCR) analysis did not show significant changes on ADA gene expression after the UCS exposure. The brain ATP metabolism showed a marked increase in adenosine levels (ADO) in animals exposed to UCS. These data suggest an increase on extracellular adenosine levels in zebrafish brain. Since this nucleoside has neuromodulatory and anxiolytic effects, changes in adenosine levels could play a role in counteracting the stress, which could be related to a compensatory mechanism in order to restore the homeostasis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Unpredictable Chronic Stress Alters Adenosine Metabolism in Zebrafish Brain

et al. 2015

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“…Adenosine receptors have been subdivided into four subtypes: A 1 , A 2A , A 2B , and A 3 . After chronic mild stress, the increase in A 1 and A 2A adenosine receptor binding in rat hippocampus and striatum was linked with depressive symptoms (Crema et al, 2013). Interestingly, adenosine and its metabolite inosine reduced immobility time in the forced swim test and tail suspension test in mice (Kaster et al, 2004(Kaster et al, , 2013.…”

Section: Introductionmentioning

confidence: 99%

The role of purinergic and dopaminergic systems on MK-801-induced antidepressant effects in zebrafish

Silva

Siebel²,

Bonan

2015

Pharmacology Biochemistry and Behavior

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“…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].…”

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confidence: 99%

“…These models make testing many factors involved in the pathogenesis, etiology, symptomatology, and the pharmacological treatment of depression possible [2].…”

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confidence: 99%

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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The effect of unpredictable chronic mild stress on depressive-like behavior and on hippocampal A1 and striatal A2A adenosine receptors

Cited by 44 publications

References 57 publications

Unpredictable Chronic Stress Alters Adenosine Metabolism in Zebrafish Brain

Unpredictable Chronic Stress Alters Adenosine Metabolism in Zebrafish Brain

The role of purinergic and dopaminergic systems on MK-801-induced antidepressant effects in zebrafish

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

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