Post-weaning Environmental Enrichment in Male CD-1 Mice: Impact on Social Behaviors, Corticosterone Levels and Prefrontal Cytokine Expression in Adulthood

Abstract

Environmental enrichment is typically associated with enhanced well-being, improved cognitive function and stress resilience. However, in some instances grouping adult male mice in enriched conditions promoted a stressful environment, which resulted in elevated endocrine, monoamine and inflammatory outcomes in response to subsequent stressor exposure. The current investigation examined whether raising male mice in an enriched environment (EE) would modulate social and anxiety-like behaviors in early adulthood and influence brain expression of pro-inflammatory cytokines and brain-derived neurotrophic factor (BDNF). Immediately after weaning (postnatal day [PD] 21), CD-1 male mice were housed with their siblings (3/cage) for 6 weeks in an EE or a standard (SE) environment. Body weights and aggressive interactions were monitored weekly. Social avoidance behaviors in the social interaction test and anxiety-like behaviors in the elevated-plus maze were examined in early adulthood. Ninety minutes following the behavioral tests, mice were sacrificed and a blood sample and the prefrontal cortex (PFC) were collected for the determination of plasma corticosterone levels as well as cytokine and BDNF mRNA expression. Mice raised in an EE exhibited more wounds and gained less weight than mice housed in a SE. Enriched mice also spent a greater amount of time in proximity of a social target in the social interaction test and made fewer transitions into the closed arms of the elevated-plus maze. Interestingly, the elevated plasma corticosterone and upregulated prefrontal interleukin (IL)-1β expression observed after the social interaction test among the SE mice were not apparent among those housed in an EE. Enrichment also increased prefrontal BDNF expression, especially among mice that experienced the social interaction test. These results suggest that although raising male mice in an EE may elicit aggressive interactions between sibling cage-mates (as indicated by a high number of wounds), this environment also enhances social behaviors and limits the corticosterone and cytokine impacts of mild social stressors encountered in early adulthood.

Environmental Enrichment Enhances Cav 2.1 Channel-Mediated Presynaptic Plasticity in Hypoxic–Ischemic Encephalopathy

“…Although the raw scores were not significantly different among the three groups, the HI EE group and NOR intact group had significantly fewer total entries than the HI control group (** p < 0.01, * p < 0.05). This result is similar to the maze results of previous studies, and indicates that long-term exposure to EE may decrease levels of anxiety, as indicated by the significantly low number of total entries [49,50]. Overall, HI EE mice and NOR intact mice had a significantly higher alterative behavior percent compared to that of HI control mice (* p < 0.05, ** p < 0.01, The HI EE group and the NOR group significantly outperformed the HI control group throughout the study period.…”

The Social Component of Environmental Enrichment Is a Pro-neurogenic Stimulus in Adult c57BL6 Female Mice

“…Animals were housed at the Centro de Biología Molecular “Severo Ochoa” (CBMSO) in a specific pathogen-free colony facility in accordance with European Community Guidelines (directive 86/609/EEC) and handled following European and local animal care protocols. Given that the hierarchy/dominance relationships established between male mice have a negative impact on AHN (Kozorovitskiy and Gould, 2004; McQuaid et al, 2018), only female mice were used in this work in all the housing conditions tested. Animals were left undisturbed for 2 weeks before starting any experimental manipulation.…”

“…In this case, one of the compartments held a non-familiar female mouse. The percentage of time the animals spent interacting with this mouse (either relative to the total exploratory or the total testing time) was calculated as a measurement of social interaction (McQuaid et al, 2018).…”

Behavioral impact of experience based on environmental enrichment: Influence of age and duration of exposure in male NMRI mice

“…The need to evaluate how agonistic interactions and dominant-subordinate relationships in male rodents may change as a consequence of being housed in EE has been highlighted in different reports (Cao et al, 2017;Giles et al, 2018;Hutchinson et al, 2012;Lima & Spinelli de Oliveira, 2014;Van Loo et al, 2003). Some studies have suggested that the presence of novel objects in the cage and the complexity of the environment enhance aggressive behaviors due to the competition for resources or physical proximity between animals (Abou-Ismail, 2011;Giles et al, 2018;McQuaid et al, 2013;McQuaid et al, 2018), the elimination of territorial odor-marking or failure to control the environment (Kaliste et al, 2006;Van Loo et al, 2001). Previous studies have indicated that male NMRI mice maintained in EE for 4 weeks display enhanced sociability and increased agonistic behaviors (Mesa-Gresa et al, 2013a).…”