Loss of Environmental Enrichment Elicits Behavioral and Physiological Dysregulation in Female Rats

Abstract

Chronic stress drives behavioral and physiological changes associated with numerous psychiatric disease states. In rodents, the vast majority of chronic stress models involve imposition of external stressors, whereas in humans stress is often driven by internal cues, commonly associated with a sense of loss. We previously exposed groups of rats to environmental enrichment (EE) for a protracted period (1 month), followed by removal of enrichment (ER), to induce an experience of loss in male rats. ER enhanced immobility in the forced swim test (FST), led to hypothalamic pituitary adrenal (HPA) axis hypoactivity, and caused hyperphagia relative to continuously enriched (EE), single-housed (Scon) and pair-housed (Pcon) groups, most of which were reversible by antidepressant treatment (Smith et al., 2017). Here, we have applied the same approach to study enrichment loss in female rats. Similar to the males, enrichment removal in females led to an increase in the time spent immobile in the FST and increased daytime food intake compared to the single and pair-housed controls. Unlike males, ER females showed decreased sucrose preference, and showed estrus cycle-dependent HPA axis hyperactivity to an acute restraint stress. The increase in passive coping (immobility), anhedonia-like behavior in the sucrose preference test and HPA axis dysregulation suggest that enrichment removal produces a loss phenotype in females that differs from that seen in males, which may be more pronounced in nature.

Hidden Talents: Poly (I:C)-induced maternal immune activation improves mouse visual discrimination performance and reversal learning in a sex-dependent manner

“…Although both SD and EE animals were subjected to the deprivation of the social component, social isolation impacted the cognitive performance in EE mice more negatively. This is consistent with data showing that loss of enrichment changes the behavioral and physiological phenotypes of animals that had been exposed to long-term EE (Morano et al, 2019). Specifically, single housing following prolonged EE exposure was associated with increased weight gain, elevated helplessness and passive coping behaviors, and blunted hypothalamic-pituitary-adrenocortical activity (Morano et al, 2019; Smith et al, 2017).…”

“…Although EE has been implicated in delaying the appearance of symptoms associated with certain brain disorders (Chourbaji et al, 2011; Herring et al, 2009; Van Dellen et al, 2000), it also makes individuals that are exposed to EE more vulnerable to its loss. Indeed, when the environment changes from being enriched to more impoverished (EE removal) behavioral alterations linked to depressive symptomology emerge (Morano et al, 2019; Smith et al, 2017). Moreover, these behavioral changes are accompanied by dysregulation of the hypothalamus-pituitary-adrenal axis activity in female rats (Morano et al, 2019).…”

“…Indeed, when the environment changes from being enriched to more impoverished (EE removal) behavioral alterations linked to depressive symptomology emerge (Morano et al, 2019; Smith et al, 2017). Moreover, these behavioral changes are accompanied by dysregulation of the hypothalamus-pituitary-adrenal axis activity in female rats (Morano et al, 2019). EE removal may therefore be considered as a second hit factor which could potentially reinforce the disruptions induced by the first hit (e.g., MIA) in early-life and ultimately lead to onset of a full clinical syndrome.…”

Environmental enrichment prevents chronic stress‐induced brain‐gut axis dysfunction through a GR‐mediated mechanism in the central nucleus of the amygdala

“…Moreover, multiple CBT sessions are typically required before patients begin seeing significant improvements in pain sensitivity, suggesting that increasing the duration of exposure to EE may be required to prevent stress‐induced pain behavior. Several reports showed that housing animals in SH cages, after being exposed to EE, induces a depressive‐like phenotype . In this regard, our animals did not develop visceral or somatic hypersensitivity after being housed in SH at the end of the WAS period.…”

Environmental influences on placental programming and offspring outcomes following maternal immune activation

“…These findings highlight the difficulty in dissociating the effects of EE from parental care to test if enrichment exposure during a particular developmental period is sufficient to offset the long-term effects of MIA in offspring. This task is challenged further by data showing that EE removal (and replacement into SD conditions) may simulate the experience of loss, inducing a depressive-like pheonotype (Smith et al, 2017;Morano et al, 2019). When EE is removed from dams, this may increase maternal care as a form of stimulation replacement (Rosenfeld and Weller 2012;Cutuli et al, 2018).…”