The depressive-like behaviors are correlated with decreased phosphorylation of mitogen-activated protein kinases in rat brain following chronic forced swim stress

Qi, Xiaoli; Lin, Wei; Li, Junfa; Pan, Yuqin; Wang, Weiwen

doi:10.1016/j.bbr.2006.08.035

Cited by 131 publications

(83 citation statements)

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“…Rather, U0126 further decreased the immobility time both in wild-type and in knockout mice. These findings suggested that ERK mediated depressant actions (Manji and Chen, 2002;Fumagalli et al, 2005) via the hippocampus and antidepressant actions (Feng et al, 2003;Duman et al, 2007;Qi et al, 2006) via other brain sites. Using acute treatments as employed here, it was recently reported that ERK is also depressant within the amygdala (Huang and Lin, 2006).…”

Section: Discussionmentioning

confidence: 87%

“…Rodent and human studies have suggested a role for the extracellular signal-regulated kinase (ERK) in depressivelike behaviors with the prefrontal cortex and hippocampus as the most likely neuroanatomical sites of ERK action (Dwivedi et al, 2001;Fumagalli et al, 2005;Qi et al, 2006). However, most studies performed so far have employed systemic injections of ERK inhibitors (Einat and Manji, 2006), and thus the selective contribution of ERK or its other upstream activators in either brain region has not been elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Regulatory Mechanisms of Fear Extinction and Depression-Like Behavior

Tronson

Schrick

Fischer

et al. 2007

Neuropsychopharmacol

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Human anxiety is frequently accompanied by depression, and when they co-occur both conditions exhibit greater severity and resistance to treatment. Little is known, however, about the molecular processes linking these emotional and mood disorders. Based on previously reported phosphorylation patterns of extracellular signal-regulated kinase (ERK) in the brain, we hypothesized that ERK's upstream activators intertwine fear and mood regulation through their hippocampal actions. We tested this hypothesis by studying the upstream regulation of ERK signaling in behavioral models of fear and depression. Wild-type and ERK1-deficient mice were used to study the dorsohippocampal actions of the putative ERK activators: mitogen-activated and extracellular signal-regulated kinase (MEK), protein kinase C (PKC), and cAMP-dependent protein kinase (PKA). Mice lacking ERK1 exhibited enhanced fear extinction and reduced depression caused by overactivation of ERK2. Both behaviors were reversed by inhibition of MEK, however the extinction phenotype depended on hippocampal, whereas the depression phenotype predominantly involved extrahippocampal MEK. Unexpectedly, inhibition of PKC accelerated extinction and decreased depression by ERK-independent mechanisms, whereas inhibition of PKA did not produce detectable molecular or behavioral effects in the employed paradigm. These results indicate that, contrary to fear conditioning but similar to mood stabilization, extinction of fear required upregulation of MEK/ERK and downregulation of ERK-independent PKC signaling. The dissociation of these pathways may thus represent a common mechanism for fear and mood regulation, and a potential therapeutic option for comorbid anxiety and depression.

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Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Regulatory Mechanisms of Fear Extinction and Depression-Like Behavior

Tronson

Schrick

Fischer

et al. 2007

Neuropsychopharmacol

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“…In addition, we evaluated the expression levels of the mitogenactivated protein kinase extracellular signal-regulated kinase 1/2 (ERK1/2) in different brain regions. We focused on ERK1/2 because it plays an important role as an effector molecule in the actions of CRF in different brain regions, including the hippocampus and the amygdala (Refojo et al, 2005;Silberstein et al, 2009) and, in addition, because it has been suggested to play a role in stress, memory, plasticity and depression (Mazzucchelli and Brambilla, 2000;Shen et al, 2004;Qi et al, 2006;Reul and Chandramohan, 2007;Silberstein et al, 2009). …”

Section: Introductionmentioning

confidence: 99%

Personality traits in rats predict vulnerability and resilience to developing stress-induced depression-like behaviors, HPA axis hyper-reactivity and brain changes in pERK1/2 activity

Castro

Diessler

Varea

et al. 2012

Psychoneuroendocrinology

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Summary Emerging evidence indicates that certain behavioral traits, such as anxiety, are associated with the development of depression-like behaviors after exposure to chronic stress. However, single traits do not explain the wide variability in vulnerability to stress observed in outbred populations. We hypothesized that a combination of behavioral traits might provide a better characterization of an individual's vulnerability to prolonged stress. Here, we sought to determine whether the characterization of relevant behavioral traits in rats could aid in identifying individuals with different vulnerabilities to developing stress-induced depressionlike behavioral alterations. We also investigated whether behavioral traits would be related to the development of alterations in the hypothalamic-pituitary-adrenal axis and in brain activityas measured through phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) -in response to an acute stressor following either sub-chronic (2 weeks) or chronic (4 weeks) unpredictable stress (CUS). Sprague-Dawley rats were characterized using a battery of behavioral tasks, and three principal traits were identified: anxiety, exploration and activity. When combined, the first two traits were found to explain the variability in the stress responses. Our findings confirm the increased risk of animals with high anxiety developing certain depression-like behaviors (e.g., increased floating time in the forced swim test) when progressively exposed to stress. In contrast, the behavioral profile based on combined low anxiety and low exploration was resistant to alterations related to social behaviors, while the high anxiety and low exploration profile displayed a particularly vulnerable pattern of physiological and neurobiological responses after sub-chronic stress exposure. Our findings indicate important differences in

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“…It is now well established that antidepressants affect different signalling pathways like that producing phosphorylation of CREB (Alboni et al, 2010;Blendy, 2006;Carreno and Frazer, 2014;First et al, 2013;Kuo et al, 2013;Reus et al, 2011). Previous researches indicated that the ERK-CREB signal system may be involved in the molecular mechanism of depression (Qi et al, 2006) and some antidepressant therapies increase both phosphorylated ERK and CREB levels in brain of rodents after repeated treatment (Carreno and Frazer, 2014;Musazzi et al, 2010;Qi et al, 2008;Tardito et al, 2009). Wherever, while early peak of ERK activation is commonly observed, CREB phosphorylation is generally seen only after days or weeks after antidepressant treatment (Di Benedetto et al, 2012).…”

Section: Ctrlmentioning

confidence: 99%

ERK1/2 phosphorylation is involved in the antidepressant-like action of 2,5-diphenyl-3-(4-fluorophenylseleno)-selenophene in mice

Gai

Sanna

Stein

et al. 2014

European Journal of Pharmacology

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a b s t r a c tWe investigated the antidepressant-like action of 5 compounds belonging to the selenophene class. The involvement of ERK and CREB activation in this action was also demonstrated. In the experiment 1, timecourse and dose-response effect of H-DPS, CH 3 -DPS, Cl-DPS, F-DPS and CF 3 -DPS were accompanied in the mouse forced swimming test (FST). Firstly, animals received compounds at a dose of 50 mg/kg, by intragastric (i.g.) route, at different times (15-240 min) before test. Results showed that the peak of maximum anti-despair behavior induced by Cl-DPS, F-DPS and CF 3 -DPS was at 30 min; maximum effect of H-DPS and CH 3 -DPS was found at 60 min, which was maintained until 120 min. Regarding doseresponse effect, all compounds reduced immobility time and increased latency for the first episode of immobility at a dose of 50 mg/kg. In addition, F-DPS also showed antidepressant-like action at a dose of 25 mg/kg, whilst H-DPS, CH 3 -DPS, Cl-DPS and CF 3 -DPS were not effective at lower doses. Thus, F-DPS was chosen for further investigation of its mechanism of action. Experiment 2 showed that treatment of animals with F-DPS (50 mg/kg, i.g.) significantly increased phosphorylated ERK1/2 levels in the prefrontal cortex and hippocampus; however, pCREB levels were not affected. Additionally, in the experiment 3 anti-immobility effect of F-DPS was completely blocked by pretreatment of animals with PD 98,059, an inhibitor of ERK phosphorylation, suggesting that ERK signalling activation is involved in its antidepressant-like action in mice. Together our data appoint F-DPS as a promising molecule for the development of a new antidepressant therapy.

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The depressive-like behaviors are correlated with decreased phosphorylation of mitogen-activated protein kinases in rat brain following chronic forced swim stress

Cited by 131 publications

References 50 publications

Regulatory Mechanisms of Fear Extinction and Depression-Like Behavior

Regulatory Mechanisms of Fear Extinction and Depression-Like Behavior

Personality traits in rats predict vulnerability and resilience to developing stress-induced depression-like behaviors, HPA axis hyper-reactivity and brain changes in pERK1/2 activity

ERK1/2 phosphorylation is involved in the antidepressant-like action of 2,5-diphenyl-3-(4-fluorophenylseleno)-selenophene in mice

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