Behavioural characterisation of chronic unpredictable stress based on ethologically relevant paradigms in rats

Sequeira‐Cordero, Andrey; Salas-Bastos, A.; Fornaguera, Jaime; Brenes, Juan C.

doi:10.1038/s41598-019-53624-1

Cited by 92 publications

(69 citation statements)

References 113 publications

(183 reference statements)

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“…The most obvious feature of CMS that the animals manifest is anhedonia [ 106 , 107 ], demonstrated by sucrose intake and preference, which is reversed by chronic, but not by acute, antidepressant treatment [ 110 ]. Rodents exposed to CMS also exhibited hyperlocomotion in the open field test [ 107 ], shorter time spent in the open arm in EPM [ 108 ], and prolonged immobility time in the FST [ 109 ]. The CMS paradigm induces altered regulation of the hypothalamus–pituitary–adrenal (HPA) axis, changes in serotonergic, noradrenergic and dopaminergic systems, and reduced hippocampal BDNF level (details are reviewed by Hill et al) [ 111 ].…”

Section: Models Of Depressionmentioning

confidence: 99%

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Animal Models of Depression: What Can They Teach Us about the Human Disease?

2021

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Depression is apparently the most common psychiatric disease among the mood disorders affecting about 10% of the adult population. The etiology and pathogenesis of depression are still poorly understood. Hence, as for most human diseases, animal models can help us understand the pathogenesis of depression and, more importantly, may facilitate the search for therapy. In this review we first describe the more common tests used for the evaluation of depressive-like symptoms in rodents. Then we describe different models of depression and discuss their strengths and weaknesses. These models can be divided into several categories: genetic models, models induced by mental acute and chronic stressful situations caused by environmental manipulations (i.e., learned helplessness in rats/mice), models induced by changes in brain neuro-transmitters or by specific brain injuries and models induced by pharmacological tools. In spite of the fact that none of the models completely resembles human depression, most animal models are relevant since they mimic many of the features observed in the human situation and may serve as a powerful tool for the study of the etiology, pathogenesis and treatment of depression, especially since only few patients respond to acute treatment. Relevance increases by the fact that human depression also has different facets and many possible etiologies and therapies.

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Section: Models Of Depressionmentioning

confidence: 99%

“…Induces both anxiety- and depression-like behaviors in FST, EPM, and sucrose preference tests [ 104 , 105 , 106 , 107 , 108 , 109 ].…”

Section: Tablementioning

confidence: 99%

Animal Models of Depression: What Can They Teach Us about the Human Disease?

2021

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“…Conditions for real-time reverse transcriptionquantitative polymerase chain reaction (RT-qPCR) were validated in a Rotor-Gene Q (QIAgen, Germany) according to published criteria (Raymaekers et al, 2009). Relative gene expression was determined by the comparative method with hypoxanthine phosphoribosyltransferase 1 (HPRT1) as a reference gene, which has been widely validated and used for the study of gene expression in rat brain tissues after several experimental conditions (Bonefeld et al, 2008;Santos and Duarte, 2008;Julian et al, 2014;Chapman and Waldenström, 2015;Sequeira-Cordero et al, 2019). In our hands, the use of other reference genes has been discouraged (e.g., actin or glyceraldehyde-3-phosphate dehydrogenase, GAPH) as they can be modified by the housing conditions (unpublished results).…”

Section: Gene Expression Analysismentioning

confidence: 99%

Neurobehavioral Effects of Restricted and Unpredictable Environmental Enrichment in Rats

2020

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To study how motivational factors modulate experience-dependent neurobehavioral plasticity, we modify a protocol of environmental enrichment (EE) in rats. We assumed that the benefits derived from EE might vary according to the level of incentive salience attributed to it. To enhance the rewarding properties of EE, access to the EE cage varied randomly from 2 to 48 h for 30 days (REE). The REE group was enriched only 50% of the time and was compared to standard housing and continuous EE (CEE) groups. As behavioral readout, we analyzed the spontaneous activity and the ultrasonic vocalizations (USVs) within the EE cage weekly, and in the open field test at the end of the experiment. In the cage, REE increased the utilization of materials, physical activity, and the rate of appetitive USVs. In the OF, the CEE-induced enhancements in novelty habituation and social signaling were equaled by the REE. At the neural level, we measured the expression of genes related to neural plasticity and epigenetic regulations in different brain regions. In the dorsal striatum and hippocampus, REE upregulated the expression of the brainderived neurotrophic factor, its tropomyosin kinase B receptor, and the DNA methyltransferase 3A. Altogether, our results suggest that the higher activity within the cage and the augmented incentive motivation provoked by the REE boosted its neurobehavioral effects equaling or surpassing those observed in the CEE condition. As constant exposures to treatments or stimulating environments are virtually impossible for humans, restricted EE protocols would have greater translational value than traditional ones.

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“…Chronic stress regimens (CVS, chronic unpredictable stress, and chronic mild stress) are commonly used in rodents to model anxiety-like avoidance behaviors (Kaufmann & Brennan, 2018;Lezak et al, 2017;Sequeira-Cordero et al, 2019) and depression-like passive coping (Lam et al, 2018;Molina et al, 1994;Sequeira-Cordero et al, 2019;Willner, 2017). In the current studies, we assessed the contribution of IL glutamate to chronic stress-induced avoidance and coping behaviors, in addition to fear-related associative learning.…”

Section: Behaviormentioning

confidence: 95%

Infralimbic cortical glutamate output is necessary for the neural and behavioral consequences of chronic stress

Pace

Christensen

Schackmuth

et al. 2020

Preprint

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AbstractExposure to prolonged stress is a major risk-factor for psychiatric disorders such as generalized anxiety and major depressive disorder (MDD). Human imaging studies have identified structural and functional abnormalities in the prefrontal cortex of MDD patients, particularly Brodmann’s area 25 (BA25). Further, deep brain stimulation of BA25 reduces symptoms of treatment-resistant depression. The rat homolog of BA25 is the infralimbic cortex (IL), which is critical for cognitive appraisal, executive function, and physiological stress reactivity. Previous studies indicate that the IL undergoes stress-induced changes in excitatory/inhibitory balance culminating in reduced activity of glutamate output neurons. However, the regulatory role of IL glutamate output in mood-related behaviors after chronic variable stress (CVS) is unknown. Here, we utilized a lentiviral-packaged small-interfering RNA to reduce translation of vesicular glutamate transporter 1 (vGluT1 siRNA), thereby constraining IL glutamate output. This viral-mediated gene transfer was used in conjunction with a quantitative anatomical analysis of cells expressing the stable immediate-early gene product ΔFosB, which accumulates in response to repeated neural activation. Through assessment of ΔFosB-expressing neurons across the frontal lobe in adult male rats, we mapped regions altered by chronic stress and determined the coordinating role of the IL in frontal cortical plasticity. Specifically, CVS-exposed rats had increased density of ΔFosB-expressing cells in the IL and decreased density in the anterior insula. The later effect was dependent on IL glutamate output. Next, we examined the interaction of CVS and reduced IL glutamate output in behavioral assays examining coping, anxiety-like behavior, associative learning, and nociception. IL glutamate knockdown decreased immobility during the forced swim test compared to GFP controls, both in rats exposed to CVS as well as rats without previous stress exposure. Further, vGluT1 siRNA prevented CVS-induced avoidance behaviors, while also reducing risk aversion and passive coping. Ultimately, this study identifies the necessity of IL glutamatergic output for regulating frontal cortical neural activity and behavior following chronic stress. These findings also highlight how disruption of excitatory/inhibitory balance within specific frontal cortical cell populations may impact neurobehavioral adaptation and lead to stress-related disorders.

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Behavioural characterisation of chronic unpredictable stress based on ethologically relevant paradigms in rats

Cited by 92 publications

References 113 publications

Animal Models of Depression: What Can They Teach Us about the Human Disease?

Animal Models of Depression: What Can They Teach Us about the Human Disease?

Neurobehavioral Effects of Restricted and Unpredictable Environmental Enrichment in Rats

Infralimbic cortical glutamate output is necessary for the neural and behavioral consequences of chronic stress

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