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Objectives: The chronic social defeat stress (CSDS) mouse model is a potentially useful system for understanding stress responses to social environments. We previously developed a mouse model of subchronic and mild social defeat stress (sCSDS) that exhibits increased body weight gain and food intake following polydipsia-like features. sCSDS mice also show avoidance behavior in a social interaction test. In this study, we examined the effects of diet quality on susceptibility to sCSDS by feeding these mice semi- and non-purified diets. Methods: Male C57BL/6J (B6; n = 82) mice were exposed to sCSDS using male ICR mice. The B6 mice were divided into four test groups: semi-purified pellet diet + sCSDS, non-purified pellet diet + sCSDS, semipurified diet + control (no sCSDS), and non-purified diet + control. Results: Although increased body weight, and food and water intake following sCSDS exposure were consistently observed in the groups that were fed semi- and non-purified diets, social avoidance behavior was influenced by food type (i.e., sCSDS mice fed semi-purified diet showed the greatest social avoidance behavior). In addition, the rates of stress susceptibility were estimated at 73.9 and 34.8% in sCSDS mice fed semi-purified and non-purified diets, respectively (P < 0.05). For comparison, the susceptible-like phenotype rates were estimated at 12.5 and 8.3% in healthy control mice fed semipurified and non-purified diets, respectively. Discussion: These results suggest that diet quality affects the vulnerability of mice to social defeat stress. [ABSTRACT FROM AUTHOR]

Social stress may precipitate psychiatric disorders such as depression, which is related to the occurrence of the metabolic syndrome, including obesity and type 2 diabetes. We have evaluated the effects of social stress on central and peripheral metabolism using a model of depression in mice. In the present study, we focused on coenzyme A (CoA) molecular species [i.e. non-esterified CoA (CoASH), acetyl-CoA and malonyl-CoA] which play important roles in numerous metabolic pathways, and we analyzed changes in expression of these molecules in the hypothalamus and liver of adult male mice (C57BL/6J) subjected to 10 days of subchronic mild social defeat stress (sCSDS) with ICR mice as aggressors. Mice (n = 12) exposed to showed hyperphagia- and polydipsia-like symptoms and increased body weight gain compared with control mice which were not affected by exposure to ICR mice (n = 12). To elucidate the underlying metabolic features in the sCSDS model, acetyl-CoA, malonyl-CoA and CoASH tissue levels were analyzed using the acyl-CoA cycling method. The levels of hypothalamic malonyl-CoA, which decreases feeding behavior, were not influenced by sCSDS. However, sCSDS reduced levels of acetyl-CoA, malonyl-CoA and total CoA (sum of the three CoA molecular species) in the liver. Hence, hyperphagia-like symptoms in sCSDS mice evidently occurred independently of hypothalamic malonyl-CoA, but might consequently lead to down-regulation of hepatic CoA via altered expression of nudix hydrolase 7. Future studies should investigate the molecular mechanism(s) underlying the down-regulation of liver CoA pools in sCSDS mice. [ABSTRACT FROM PUBLISHER]

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]

We developed a novel method to evaluate the nest-building behavior of mice using an inexpensive depth camera. The depth camera clearly captured nest-building behavior. Using three-dimensional information from the depth camera, we obtained objective features for assessing nest-building behavior, including “volume,” “radius,” and “mean height”. The “volume” represents the change in volume of the nesting material, a pressed cotton square that a mouse shreds and untangles in order to build its nest. During the nest-building process, the total volume of cotton fragments is increased. The “radius” refers to the radius of the circle enclosing the fragments of cotton. It describes the extent of nesting material dispersion. The “radius” averaged approximately 60 mm when a nest was built. The “mean height” represents the change in the mean height of objects. If the nest walls were high, the “mean height” was also high. These features provided us with useful information for assessment of nest-building behavior, similar to conventional methods for the assessment of nest building. However, using the novel method, we found that JF1 mice built nests with higher walls than B6 mice, and B6 mice built nests faster than JF1 mice. Thus, our novel method can evaluate the differences in nest-building behavior that cannot be detected or quantified by conventional methods. In future studies, we will evaluate nest-building behaviors of genetically modified, as well as several inbred, strains of mice, with several nesting materials. [ABSTRACT FROM AUTHOR]

Tameness is a major element of animal domestication and involves two components: motivation to approach humans (active tameness) and reluctance to avoid humans (passive tameness). To understand the behavioral and genetic mechanisms of active tameness in mice, we had previously conducted selective breeding for long durations of contact and heading toward human hands in an active tameness test using a wild‐derived heterogeneous stock. Although the study showed a significant increase in contacting and heading with the 12th generation of breeding, the effect on other behavioral indices related to tameness and change of gene expression levels underlying selective breeding was unclear. Here, we analyzed nine tameness‐related traits at a later stage of selective breeding and analyzed how gene expression levels were changed by the selective breeding. We found that five traits, including contacting and heading, showed behavioral change in the selective groups comparing to the control through the generations. Furthermore, we conducted cluster analyses to evaluate the relationships among the nine traits and found that contacting and heading combined in an independent cluster in the selected groups, but not in the control groups. RNA‐Seq of hippocampal tissue revealed differential expression of 136 genes between the selection and control groups, while the pathway analysis identified the networks associated with these genes. These results suggest that active tameness was hidden in the control groups but became apparent in the selected populations by selective breeding, potentially driven by changes in gene expression networks. [ABSTRACT FROM AUTHOR]