The lonely mouse: verification of a separationinduced model of depression in female mice. Behav Brain Res

Psychology Department and Neuroscience Institute, Dalhousie University, Halifax, Nova Scotia, Canada, B3H 4J1
Behavioural brain research (Impact Factor: 3.03). 02/2010; 207(1):196-207. DOI: 10.1016/j.bbr.2009.10.006


Animal models of depression seldom test females, even though women are twice as likely as men to suffer from major depressive disorder. Since female mice are sensitive to social isolation, we tested a separation-based model of depression in three experiments. In experiment 1 female C57BL/6J mice were housed in three conditions: isolated (housed individually from 8 weeks of age), separated (housed in groups and then separated and housed individually at 23 weeks of age) and grouped (housed in groups from 8 weeks of age). At 24 weeks of age, there was a significant increase in weight and in immobility in individually housed mice in the forced swim test (FST) and tail suspension test (TST), a reduction in transitions in the L/D box, a reduced startle response and reduced prepulse inhibition, but no differences in cued or context fear conditioning. Experiment 2 showed that fluoxetine treatment administered via drinking water attenuated depressive-like behaviour in the FST and TST in individually housed female C57BL/6J mice, but had no effect on anxiety-like behaviour. Experiment 3 found that group-housed females had higher baseline corticosterone (CORT) levels than isolated females and fluoxetine had no effect on CORT levels. Thus, separation from group housing is a reliable and valid method for inducing depression-like behaviour in female mice. This procedure is both versatile, allowing for the study of genetic and environmental interactions, and accessible, making it useful for studying depression and testing new drugs for its treatment.

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    • "We next performed a similar experiment but in this case the cells generated one week before training were labeled using a GFP-expressing retrovirus (Table 2, Batch 5, Fig. 2H). Given that the effect of learning on cell survival has been shown to be more pronounced in female rats compared to male (Dalla et al., 2009) and that individual housing (Martin and Brown, 2010) may reduce the ability of the brain to respond to environmental challenges, female C57BL/6J mice housed in groups of 4 were used. Although female mice learned the task (Fig. 7A), dendritic tree measurements revealed no differences between "
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    ABSTRACT: New dentate granule cells (GCs) are generated in the hippocampus throughout life. These adult-born neurons are required for spatial learning in the Morris water maze (MWM). In rats, spatial learning shapes the network by regulating their number and dendritic development. Here we explored whether such modulatory effects exist in mice. New GCs were tagged using thymidine analogs or a GFP-expressing retrovirus. Animals were exposed to a reference memory protocol for 10 to 14 days (spaced training) at different times after newborn cells labeling. Cell proliferation, cell survival, cell death, neuronal phenotype and dendritic and spine development were examined using immunohistochemistry. Surprisingly, spatial learning did not modify any of the parameters under scrutiny including cell number and dendritic morphology. These results suggest that although new GCs are required in mice for spatial learning in the MWM, they are, at least for the developmental intervals analyzed here, refractory to behavioral stimuli generated in the course of learning in the MWM. This article is protected by copyright. All rights reserved. © 2015 Wiley Periodicals, Inc.
    Hippocampus 03/2015; DOI:10.1002/hipo.22438 · 4.16 Impact Factor
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    • "However, it would be interesting to assess the effects of additional types of innate, unlearned stressors after traumatic brain injury. In rodents, physical restraint [52], social isolation [53,54], predator threat exposure [55], and chronic unpredictable stress [56] paradigms can all evoke stress and avoidance responses without requiring learning. Application of these types of stressors after mild or severe TBI would help to clarify the response to different types of stress after brain injury. "
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    ABSTRACT: The debilitating effects of repetitive concussive traumatic brain injury (rcTBI) have been increasingly recognized in both military and civilian populations. rcTBI may result in significant neurological, cognitive, and affective sequelae, and is often followed by physical and/or psychological post-injury stressors that may exacerbate the effects of the injury and prolong the recovery period for injured patients. However, the consequences of post-injury stressors and their subsequent effects on social and emotional behavior in the context of rcTBI have been relatively little studied in animal models. Here, we use a mouse model of rcTBI with two closed-skull blunt impacts 24 hours apart and social and emotional behavior testing to examine the consequences of a stressor (foot shock fear conditioning) following brain injury (rcTBI). rcTBI alone did not affect cued or contextual fear conditioning or extinction compared to uninjured sham animals. In the sucrose preference test, rcTBI animals had decreased preference for sucrose, an anhedonia-like behavior, regardless of whether they experienced foot shock stress or were non-shocked controls. However, rcTBI and post-injury foot shock stress had synergistic effects in tests of social recognition and depression-like behavior. In the social recognition test, animals with both injury and shock were more impaired than either non-shocked injured mice or shocked but uninjured mice. In the tail suspension test, injured mice had increased depression-like behavior compared with uninjured mice, and shock stress worsened the depression-like behavior only in the injured mice with no effect in the uninjured mice. These results provide a model of subtle emotional behavioral deficits after combined concussive brain injury and stress, and may provide a platform for testing treatment and prevention strategies for social behavior deficits and mood disorders that are tailored to patients with traumatic brain injury.
    PLoS ONE 09/2013; 8(9):e74510. DOI:10.1371/journal.pone.0074510 · 3.23 Impact Factor
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    • "In accordance with this, many have found female rats to weigh less at the end of EE [6] [15] [27] and some have shown this effect to persist for up to three months post-enrichment [14]. Similar results have also been found in mice [22] [34]. However, even when similar paradigms are used, inconsistency in findings continues to persist. "
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    ABSTRACT: Environmental enrichment (EE) exposes laboratory animals to novelty and complexity through alterations in the physical and social environment, which lead to enhanced sensory, cognitive and physical stimulation. Housing rodents in an EE is a highly recommended practice by governing bodies regulating animal welfare due to a growing body of evidence suggesting its benefits on rodents' wellbeing and the more naturalistic environment that such housing conditions provide. However, most paradigms and hypotheses rely on information currently available from studies performed on male subjects and the information regarding the effects of EE on female rodents' behaviour and physiology is limited. Given the variety of EE paradigms described, it is increasingly difficult to ascertain the benefits or possible consequences of enriched housing strategies in females, let alone aid at establishing standardized environments in rodents. This review evaluates the female rodent literature that has examined the outcome of EE on behaviour and neurochemistry and aims at identifying key elements to be addressed by future studies. Specifically, results from cognitive behavioural tests as well as commonly used tests of emotionality will be discussed, while also evaluating their relation to changes in neurochemistry and hormones brought on by various EE paradigms. Lastly, the impact of maternal enrichment on both offspring and maternal behaviour and physiology will be reviewed.
    Behavioural brain research 07/2013; 253. DOI:10.1016/j.bbr.2013.07.018 · 3.03 Impact Factor
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