Long-term characterization of the Flinders Sensitive Line rodent model of human depression: Behavioral and PET evidence of a dysfunctional entorhinal cortex

Thiele, Stephanie; Spehl, Timo S.; Frings, Lars; Braun, Friederike; Ferch, M.; Rezvani, Amir H.; Furlanetti, Luciano; Meyer, Philipp T.; Coenen, Volker A.; Döbrössy, Máté

doi:10.1016/j.bbr.2015.11.026

Cited by 18 publications

(16 citation statements)

References 61 publications

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“…Most of the speculation concerning the mechanisms of mfb DBS looks towards the direct or indirect modulation of the mesocorticolimbic dopaminergic reward/motivational systems; however, it could equally well modulate the hippocampal formation and associated structures via connections between the VTA and the entorhinal cortex. We have shown using 18‐FDG microPET that FSL rats have a robust and long‐term bilateral hypometabolism in this structure, and the entorhinal cortex has been implicated in clinical depression too (Gerritsen et al., 2011; Thiele et al., 2016). The entorhinal cortex sub‐serves spatial navigation, acquisition and consolidation of declarative memory by encoding spatial/directional/temporal data and the hippocampus integrates this information within the given spatial and temporal context (Jacobs et al., 2010; Knierim, 2015; Witter et al., 2017).…”

Section: Discussionmentioning

confidence: 99%

“…An initial, and extensive behavioural characterization of the FSL described some of the phenotypes to be transient (i.e., not helpful in long‐term studies), but others, such as weight change, reduced drive and motivation, and increased anxiety or cognitive, learning and memory deficits as long‐term/robust impairments. Furthermore, FSL animals also exhibited bilateral chronic hypometabolism—as measured by 18‐FDG PET—in the entorhinal cortex, a structure crucial in encoding spatial and non‐spatial information and the formation of declarative memory (Thiele et al., 2016). Next, we assessed the range of behavioural modification achieved by mfb DBS in the FSL rats.…”

Section: Experimental Mfb Dbsmentioning

confidence: 99%

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Neuromodulation in Psychiatric disorders: Experimental and Clinical evidence for reward and motivation network Deep Brain Stimulation: Focus on the medial forebrain bundle

Döbrössy¹,

Chockalingam²,

Vajari

et al. 2020

Eur J of Neuroscience

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Section: Discussionmentioning

confidence: 99%

Section: Experimental Mfb Dbsmentioning

confidence: 99%

Neuromodulation in Psychiatric disorders: Experimental and Clinical evidence for reward and motivation network Deep Brain Stimulation: Focus on the medial forebrain bundle

Döbrössy¹,

Chockalingam²,

Vajari

et al. 2020

Eur J of Neuroscience

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“…The elevated headshakes in females were surprising given recent reports of substantially higher headshakes in males (Kokras, Polissidis, Antoniou, & Dalla, 2017). These seemingly contradictory findings could be due to strain differences because Kokras et al performed their analyses in the Flinders Sensitive Line, a strain predisposed to depressive-like behaviors (Ardalan, Wegener, Polsinelli, Madsen, & Nyengaard, 2016; Thiele et al, 2016). What these differences signify on a motivational level is difficult at this point to speculate.…”

Section: Discussionmentioning

confidence: 99%

Strain-dependent sex differences in a long-term forced swim paradigm.

Colom-Lapetina

Begley

Johnson

et al. 2017

Behavioral Neuroscience

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Women are twice as likely as men to suffer from trauma- and stressor-related disorders. The development of improved therapeutic interventions is contingent upon a more complete grasp of both the neural and behavioral dynamics of the stress response in females. The rodent forced swim test (FST) is a valuable animal model for exploring the neurobiological mechanisms responsible for selection of active and passive responses to inescapable stressors, but it is often neglected in 2-day FST studies is the dissociation of innate (Day 1) versus learned (Day 2) coping responses. Here, we used a modified, long-term (4-week) FST paradigm and immunohistological analysis to study the interactions of sex, strain, and housing arrangement on selection of active and passive coping strategies in Sprague Dawley (SD) and Long Evans (LE) rats. We observed significant strain × sex interactions in both forced swim sessions with respect to both passive (immobility) and active (climbing and headshakes) responses. In immobility measures, we observed stable sex differences in SD rats and a stable lack of sex differences in LE rats across tests. In addition, both SD and LE females displayed significantly more headshakes than males during Test 1 and more climbing in Test 2. Most notably, males, but not females, exhibited a cross-test increase in immobility, suggesting that males and females may engage different learning processes in a 2-day FST. These sex differences corresponded to c-fos expression in the medial prefrontal cortex (mPFC), indicating that the mPFC may contribute to sexually dimorphic behavior in the FST. (PsycINFO Database Record

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“…For example, Flinders sensitive line (FSL) rats display both depression-like behavior (121) and vulnerability to stressinduced anhedonia-like behavior (122). These behavioral traits are also associated with elevated corticosterone levels (123)(124)(125). Wistar-Kyoto (WKY) rats are characterized by depression-like and anxiety-like behaviors (126), and exhibit an upregulated basal serum corticosterone level at the start of the dark cycle, which is reminiscent of the circadian rhythm abnormalities seen in human MDD (127,128).…”

Section: Corticosterone Levels In Genetic Models Of Depressionmentioning

confidence: 99%

Cortisol and Major Depressive Disorder—Translating Findings From Humans to Animal Models and Back

Nandam¹,

Brazel²,

Zhou³

et al. 2020

Front. Psychiatry

156

103

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Major depressive disorder (MDD) is a global problem for which current pharmacotherapies are not completely effective. Hypothalamic-pituitary-adrenal (HPA) axis dysfunction has long been associated with MDD; however, the value of assessing cortisol as a biological benchmark of the pathophysiology or treatment of MDD is still debated. In this review, we critically evaluate the relationship between HPA axis dysfunction and cortisol level in relation to MDD subtype, stress, gender and treatment regime, as well as in rodent models. We find that an elevated cortisol response to stress is associated with acute and severe, but not mild or atypical, forms of MDD. Furthermore, the increased incidence of MDD in females is associated with greater cortisol response variability rather than higher baseline levels of cortisol. Despite almost all current MDD treatments influencing cortisol levels, we could find no convincing relationship between cortisol level and therapeutic response in either a clinical or preclinical setting. Thus, we argue that the absolute level of cortisol is unreliable for predicting the efficacy of antidepressant treatment. We propose that future preclinical models should reliably produce exaggerated HPA axis responses to acute or chronic stress a priori, which may, or may not, alter baseline cortisol levels, while also modelling the core symptoms of MDD that can be targeted for reversal. Combining genetic and environmental risk factors in such a model, together with the interrogation of the resultant molecular, cellular, and behavioral changes, promises a new mechanistic understanding of MDD and focused therapeutic strategies.

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Long-term characterization of the Flinders Sensitive Line rodent model of human depression: Behavioral and PET evidence of a dysfunctional entorhinal cortex

Cited by 18 publications

References 61 publications

Neuromodulation in Psychiatric disorders: Experimental and Clinical evidence for reward and motivation network Deep Brain Stimulation: Focus on the medial forebrain bundle

Neuromodulation in Psychiatric disorders: Experimental and Clinical evidence for reward and motivation network Deep Brain Stimulation: Focus on the medial forebrain bundle

Strain-dependent sex differences in a long-term forced swim paradigm.

Cortisol and Major Depressive Disorder—Translating Findings From Humans to Animal Models and Back

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