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Psychosocial stress can cause mental conditions such as depression in humans. To develop drug therapies for the treatment of depression, it is necessary to use animal models of depression to screen drug candidates that exhibit anti-depressive effects. Unfortunately, the present methods of drug screening for antidepressants, the forced-swim test and tail-suspension test, are limiting factors in drug discovery because they are not based on the constructive validity of objective phenotypes in depression. Previously, we discovered that the onset of nest building is severely delayed in mice exposed to subchronic mild social defeat stress (sCSDS). Therefore, a novel paradigm combining acute social defeat stress (ASDS) and the nest-building test (SNB) were established for the efficient screening of drugs for depressive-like symptoms. Since ASDS severely delayed the nest-building process as shown in chronically social defeated mice, we sought to rescue the delayed nest-building behavior in ASDS mice. Injecting a specific serotonin 2a receptor antagonist (SR-46349B), the nest-building deficit exhibited by ASDS mice was partially rescued. On the other hand, a selective serotonin reuptake inhibitor (fluoxetine) did not rescue the nest-building deficit in ASDS mice. Therefore, we conclude that the SNB paradigm is an another potential behavioral method for screening drugs for depressive-like symptoms including attention deficit, anxiety, low locomotion, and decreased motivation. [ABSTRACT FROM AUTHOR]

Behavioral and physiological evaluations of animal models of depression are essential to thoroughly understand the mechanisms of depression in humans. Various models have been developed and characterized, and the socially defeated mouse has been widely used for studying depression. Here, we developed and characterized a mouse model of social aversion using a subchronic and mild social defeat stress (sCSDS) paradigm. Compared to control mice, sCSDS mice showed significantly increased body weight gain, water intake, and social aversion to dominant mice on the social interaction test. We observed nest building behavior in sCSDS mice using the pressed cotton as a nest material. Although sCSDS mice eventually successfully built nests, the onset of nest building was severely delayed compared to control mice. The underlying mechanism of this significant delay in nest building by sCSDS mice is unclear. However, our results demonstrate that nest building evaluation is a simple and useful assay for understanding behavior in socially defeated mice and screening drugs such as antidepressants. [ABSTRACT FROM AUTHOR]

Nest building is one of the innate behaviors that are widely observed throughout the animal kingdom. Previous studies have reported specific brain regions and genetic loci associated with nest building in mice. These studies mainly evaluated the nest structure, without observing the nesting process. In this study, we evaluated the effects of strain and learning on the nesting process of mice using a 3D depth camera. To determine the quality of the nest structure, a conventional scoring method, Deacon scores 1–5, was applied to the recorded depth images. The final score of the nest, latency to start nesting behavior, and latencies to reach Deacon scores 3–5, were determined using three genetically different mouse strains—C57BL/6NCrl (B6), DBA/2NCrlCrlj (DBA), and B6D2F1/Crl (B6D2F1). The final score of the DBA nest was significantly lower than that of the B6D2F1 nest, and DBA mice showed significantly longer latency to start nest building than the other two strains in the first trial. By observing the time course of nest building, we confirmed that DBA mice took significantly longer to build their nests than B6 and B6D2F1 mice. Although we did not find any significant differences between DBA and B6 mice in the final assessment of the nest based on the Deacon method, overnight monitoring of the nesting behavior using a 3D depth camera could elucidate the clear differences in the amount of time spent nesting between DBA and B6 mice. In addition, the learning effect was more evident in DBA mice than it was in B6 in terms of latencies to reach Deacon score 3–5 in five repeated trials. DBA mice showed a gradual decrease in latency to build, whereas nesting behaviors of B6 mice were relatively consistent throughout the five trials. Therefore, our 3D depth image method gives higher resolution and structural information regarding the nesting process in mice. Future genetic analyses using the 3D assessment system will provide novel insights into the complex genetic basis for nesting and other behaviors in animals. [ABSTRACT FROM AUTHOR]