Deep brain stimulation in treatment-resistant depression in mice: Comparison with the CRF1 antagonist, SSR125543

Dournes, Carine; Beeské, Sandra; Belzung, Catherine

doi:10.1016/j.pnpbp.2012.07.019

Cited by 38 publications

(33 citation statements)

References 47 publications

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“…Firstly, the mechanisms by which chronic stresses regulate the expression of these genes have not been profoundly explored in this study. Another limitation is that we only explored the dopaminergic mechanisms underlying anhedonia, passive coping behavior, and exploratory interest but have not explored many other types of depressive behaviors, such as social withdrawal, irritability, psychomotor retardation, and so on (Dournes, Beeské, Belzung, & Griebel,2013). …”

Section: Discussionmentioning

confidence: 99%

Divergent anomaly in mesocorticolimbic dopaminergic circuits might be associated with different depressive behaviors, an animal study

et al. 2017

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BackgroundThe mesocorticolimbic dopamine system, which originates from the ventral tegmental area (VTA) and projects primarily to the prefrontal cortex (PFC), olfactory tubercle (OT), nucleus accumbens (NAc), dorsal striatum (ST), and the amygdala (AMy), plays a pivotal role in determining individual motivation and sensitivity to rewards, namely, anhedonia. Not all depressive individuals exhibited anhedonia, thus, it is natural to speculate that the heterogenous manifestations of depression might be related to the mesocorticolimbic dopamine system. Maternal deprivation (MD) and chronic unpredictable stress (CUPS) are two well‐established depressogenic stressors, and they were proven to induce different depressive phenotypes.MethodsThe depressive and anxiety‐like behaviors of MD and CUPS‐treated rats were measured by classical behavioral tests including open field, forced swimming, and sucrose preference test. The expression of D1‐5 dopamine receptors and DAT mRNA and protein in the mesocorticolimbic dopamine system of rats exposed to MD and CUPS were measured by real‐time PCR and Western blot, respectively.ResultsSevere anhedonia was observed in MD but not CUPS rats. Divergent expression of D1 and D2 receptors and DAT mRNA and protein in the mesocorticolimbic dopamine system were found between MD and CUPS rats. Significant correlations between different depressive behaviors and D1‐/D2‐like receptors and DAT protein levels in the mesocorticolimbic dopamine system were observed.ConclusionDifferent depressive behaviors of rats such as anhedonia, passive coping behavior, and declined exploratory interest might be related to divergent dopaminergic pathways. Anhedonia is associated with the dysfunction of VTA‐NAc and VTA‐OT dopaminergic pathways, the passive coping behavior is related to the dysregulation of VTA‐PFC and VTA‐AMy pathways, and individual exploratory interest is associated with abnormal activity of VTA‐PFC and VTA‐ST pathways.

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Section: Discussionmentioning

confidence: 99%

Divergent anomaly in mesocorticolimbic dopaminergic circuits might be associated with different depressive behaviors, an animal study

et al. 2017

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“…We first built on previous studies of cortical DBS in the chronic mild stress model (7,31) by demonstrating the efficacy of DBS in modulating CSDS-induced social avoidance, which models another symptom of human depression. In line with our previous reports (20-22) CSDS induced a persistent social withdrawal.…”

Section: Discussionmentioning

confidence: 99%

“…For c-Fos expression experiments, mice were stimulated for 1 hour immediately followed by perfusion. For chronic DBS experiments, DBS was applied 5 hours per day for 7 days—a paradigm similar to prior chronic DBS studies for depression which have observed long-lasting antidepressant-like effects (7,29-31)—while mice remained in their home cages. Sham-stimulated mice were handled and connected to the stimulator in an identical manner, but no current was applied.…”

Section: Methodsmentioning

confidence: 99%

Antidepressant-like Effects of Cortical Deep Brain Stimulation Coincide With Pro-neuroplastic Adaptations of Serotonin Systems

Veerakumar

Challis²,

Gupta³

et al. 2014

Biological Psychiatry

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Background Cortical deep brain stimulation (DBS) is a promising therapeutic option for treatment-refractory depression but its mode of action remains enigmatic. Serotonin (5-HT) systems are engaged indirectly by ventromedial prefrontal cortex (vmPFC) DBS. Resulting neuroplastic changes in 5-HT systems could thus coincide with the long-term therapeutic activity of vmPFC DBS. Methods We tested this hypothesis by evaluating the antidepressant-like activity of vmPFC DBS in the chronic social defeat stress (CSDS) model of depression (n = 8-13 mice per group). Circuit-wide activation induced by vmPFC DBS was mapped using c-Fos immunolabeling. The effects of chronic vmPFC DBS on the physiology and morphology of genetically-identified 5-HT cells from the Dorsal Raphe Nucleus (DRN) were examined using whole-cell recording, somatodendritic 3-D reconstructions and morphometric analyses of presynaptic boutons along 5-HT axons. Results Acute DBS drove c-Fos expression locally in the vmPFC and in several distal monosynaptically-connected regions, including the DRN. Chronic DBS reversed CSDS-induced social avoidance, restored the disrupted balance of excitatory/inhibitory inputs onto 5-HT neurons, and reversed 5-HT hypoexcitability observed after CSDS. Furthermore, vmPFC DBS reversed CSDS-induced arborization of 5-HT dendrites in the DRN and increased the size and density of 5-HT presynaptic terminals in the dentate gyrus and vmPFC. Conclusions We validate a new preclinical paradigm to examine cellular mechanisms underlying the antidepressant-like activity of vmPFC DBS and identify dramatic circuit-mediated cellular adaptations which coincide with this treatment. These neuroplastic changes of 5-HT neurons may contribute to the progressive mood improvements reported in patients treated with chronic courses of cortical DBS.

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“…Furthermore, as far as we are aware, DBS has not yet been applied in these particular models to the anterior cingulate cortex, the area most frequently targeted in clinical and preclinical studies. (DBS of the cingulate cortex did, however, reverse a behavioural effect of CMS in a sub-group of mice identified empirically as resistant to chronic fluoxetine (Dournes et al 2013)). Clearly, more work is needed to establish the effectiveness of DBS of the anterior cingulate cortex in models of treatment resistance, to extend studies with ketamine and DBS to more relevant behavioural endpoints, and to examine the effects of these novel treatment modalities in a wider range of models, particularly those listed in the second section of Table 1.…”

Section: Response To Novel Antidepressantsmentioning

confidence: 98%

“…For example, deep brain stimulation (DBS) of the vm-PFC has been reported to produce long-lasting antidepressant effects in treatment-resistant depressed patients (Mayberg 2009;Hamani et al 2011;McGrath et al 2014). A rapid reversal of CMS-induced anhedonia and other depression-related behaviours has also been demonstrated in rats following DBS of the vm-PFC (Hamani et al 2012;Dournes et al 2013;Veerakumar et al 2014). For obvious reasons, DBS has not been used in antidepressant-responsive patients, but there is a reasonable expectation that it would be effective if implemented.…”

Section: A Diathesis-stress Perspectivementioning

confidence: 99%

Treatment-resistant depression: are animal models of depression fit for purpose?

2015

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Deep brain stimulation in treatment-resistant depression in mice: Comparison with the CRF1 antagonist, SSR125543

Cited by 38 publications

References 47 publications

Divergent anomaly in mesocorticolimbic dopaminergic circuits might be associated with different depressive behaviors, an animal study

Divergent anomaly in mesocorticolimbic dopaminergic circuits might be associated with different depressive behaviors, an animal study

Antidepressant-like Effects of Cortical Deep Brain Stimulation Coincide With Pro-neuroplastic Adaptations of Serotonin Systems

Treatment-resistant depression: are animal models of depression fit for purpose?

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