The lonely mouse: Verification of a separation-induced model of depression in female mice
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.
- SourceAvailable from: Hélène Plamondon[Show abstract] [Hide abstract]
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
- [Show abstract] [Hide abstract]
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
- [Show abstract] [Hide abstract]
ABSTRACT: Genetically modified mice are used to study the neurobiological basis of normal behavior and have been developed as models of human neurodegenerative and psychiatric disorders. These genetically modified mice show changes in gene expression in particular brain regions and altered behavior. The analysis of behavioral abnormalities in genetically modified mice through behavioral phenotyping is essential to determine the functional effects of genetic manipulations on the brain. Once a mouse model of a neural disorder has been established, novel treatments, including pharmacotherapy, immunotherapy, gene therapy, or behavioral therapy may be tested to restore the mouse to “normal.” However, many factors have the potential to confound the results of behavioral studies and these have led to questions about the validity and reliability of mouse models of neural disorders. The mouse itself must be considered, as issues such as the specificity of genetic manipulations, the supplier of the mice, their health, sex, and sensory or motor impairments may influence experimental findings. Environmental factors, including prenatal experience, housing conditions, and the social environment, also have the potential to affect the results. Furthermore, the laboratory environment, including the testing room, the light:dark (L:D) cycle, and the process of handling and habituating the mice to the test apparatus, may influence their behavior. The testing apparatus may lead to confounds through lack of standardization of design, poor reliability, and errors in automated recording of behavior. Finally, the experimenters themselves may influence the results because of inexperience, differences in following a protocol, and errors in recording data. This chapter outlines sources of error in the use of mouse models and suggests the ways in which these errors can be reduced to improve the reliability and validity of mouse models of human neurodegenerative and neuropsychiatric disorders.Advances in the Study of Behavior 01/2010; 41(41):255-366. DOI:10.1016/S0065-3454(10)41007-4 · 2.69 Impact Factor