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: 3.39). 02/2010; 207(1):196-207. DOI: 10.1016/j.bbr.2009.10.006

ABSTRACT 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.

    • "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 · 4.30 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 · 3.39 Impact Factor
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    • "Consistent with the increased risk for MDD in persons who are socially isolated (see above), social isolation in female animals has been shown to increase depressive-like behaviors (Grippo et al., 2007; Martin & Brown, 2010). Thus, it was predicted that tumor-bearing individually-housed mice would show more depressive-like behavior than tumor-bearing group-housed mice. "
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    ABSTRACT: Considerable data demonstrate a high prevalence of depressive symptoms in cancer patients. This study introduces an experimental model to examine the effect of tumor on depressive-like behavior. Female C57BL/6 mice were injected i.p. with syngeneic ID8 ovarian carcinoma. Experiment 1 measured sucrose intake before and after tumor incubation to assess the effect of tumor on anhedonic depressive-like behavior. Experiment 2 examined effects of tumor and social housing on anhedonia and a second depressive-like behavior, tail suspension test (TST) immobility. Systemic proinflammatory and antiinflammatory cytokines were measured following each experiment. Additional behaviors assessed the specificity of tumor's effect on depressive-like behavior. Tumor caused a reduction in sucrose intake relative to baseline and control levels (P<.05). Moreover, individually-housed tumor-bearing mice exhibited a lower sucrose preference than group-housed tumor-bearing or control mice in either housing condition (P<.05). Although tumor-bearing mice exhibited less locomotion than controls (P<.001), there was no significant effect of tumor on TST immobility. Tumor caused higher levels of systemic proinflammatory and antiinflammatory cytokines and smaller body weight (P<.05), but appetite and motor capacity were not significantly affected. Statistical mediation analysis showed that circulating interleukin-6 partially mediated the effect between tumor and home cage locomotion (P<.01) but not between tumor and sucrose intake. It is concluded that tumor elicits anhedonic depressive-like behavior in a murine model of ovarian cancer. This may have important implications for etiology of depression in the clinical cancer setting.
    Brain Behavior and Immunity 03/2011; 25(3):555-64. DOI:10.1016/j.bbi.2010.12.010 · 6.13 Impact Factor
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