Individual differences in chronically defeated male mice: Behavioral, endocrine, immune, and neurotrophic changes as markers of vulnerability to the effects of stress

Abstract

This study aimed to analyze different behavioral profiles in response to chronic social defeat using the sensorial contact model. We hypothesized that a passive profile, unlike an active one, would be associated with behavioral and physiological characteristics related to depression. Six-week-old OF1 male mice were subjected to defeat for 21 consecutive days. A combination of cluster and discriminant analyses of the behavior exhibited during confrontation on Day 21 established two behavioral profiles: active (n = 22) and passive (n = 34). Passive mice, with a high level of immobility and low non-social exploration, had higher plasma corticosterone concentrations than active mice after 21 days of defeat. Three days after the last defeat, passive mice had lower corticosterone levels than manipulated-control mice (n = 11). Higher levels of interleukin-6 and tumor necrosis factor-α (TNF-α) in the spleen and lower hippocampal brain-derived neurotrophic factor levels were observed in passive mice in comparison with those in active mice and the manipulated controls. The only differences observed in active mice in relation to the manipulated control were higher plasma corticosterone (Day 21) and TNF-α levels. The results show that different behavioral profiles in response to chronic defeat are associated with different physiological profiles, and that the passive profile presents physiological characteristics previously associated with depression.

Coping with Chronic Social Stress in Mice: Hypothalamic-Pituitary-Adrenal/ Sympathetic-Adrenal-Medullary Axis Activity, Behavioral Changes and Effects of Antalarmin Treatment: Implications for the Study of Stress-Related Psychopathologies

“…Previous studies in our laboratory using the chronic social defeat stress model revealed that subjects who adopt a passive behavioral profile, which is characterized by a higher immobility and lower social and nonsocial exploration than the active subjects, have an exaggerated corticosterone response following repeated defeat and low resting levels of corticosterone several days after the end of the chronic defeat experience [5,19]. Human studies report similar patterns in cortisol levels following prolonged periods of stress [20,21].…”

“…The behavioral evaluation was carried out using The Observer 3.0 (Noldus ITC, Wageningen, the Netherlands). To classify the subjects according to behavior, two cluster analyses were performed on all of the defeated mice based on the behavioral characteristics they displayed in the social confrontation on days 18 and 21 using the mean percentage of time spent on each assessed behavioral element [19]. …”

Anhedonic-like traits and lack of affective deficits in 18-month-old C57BL/6 mice: Implications for modeling elderly depression

“…Aging in rodents resulted in diminished place preference conditioned to a food (Rubinow et al, 2009), nicotine, cocaine, morphine and alcohol (Vastola et al, 2002;Campbell and Wood, 2000). It is also associated with lower novelty exploration (Vastola et al, 2002;Campbell and Wood, 2000) and decreased scores of grooming (Scimonelli et al, 1999;Shoji and Mizoguchi, 2011), which are considered to reflect a reduced self-rewarding activity (Pothion et al, 2004;Dubreucq et al, 2010;Gómez-Lázaro et al, 2011;Park et al, 2011). Together, these findings from animal studies parallel clinical features of elderly depression, which are predominantly related to hedonic deficits (Gallo et al, 1994(Gallo et al, , 1997.…”

Reduction of serotonergic gene expression in the raphe nuclei of the midbrain under positive fighting experience in male mice

“…It has been shown many times that the Bdnf and Creb genes are involved in the brain mechanism of chronic social defeat stress [26,[34][35][36][37][38]. At the same time, the experimental evidence of the role of these genes in the mechanisms of aggression is scarce and inconclusive.…”