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.
Highlights
The experience of loss represents a significant risk factor for affective distress and disease
In males, prolonged exposure to enrichment followed by removal to single housing results in reproducible increases in passive coping behavior, weight gain, and hypothalamic-pituitary-adrenocortical (HPA) axis hypoactivity that is not emulated by single housing alone, chronic restraint exposure or chronic variable stress, indicating that the behavioral and somatic phenotype is unique to experiencing cessation of enrichment
At 7 days post removal of enrichment, the rats were subjected to a 30 min restraint stress in order to measure HPA axis responsiveness in the form of plasma corticosterone levels (CORT) (Figure 2)
Summary
The experience of loss represents a significant risk factor for affective distress and disease. Life events connected with loss of financial resources, loved ones, relationships or liberties are among the most often reported experiences linked to negative mental health outcomes, prominently including depression and anxiety disorders (Rahe, 1968; Ganzini et al, 1990; Sikorski et al, 2014; Wang et al, 2015; Wiseman et al, 2015). There have been relatively few studies focusing on neurobiological mechanisms underlying the loss of positively rewarding life experiences. Our lab has recently developed an enrichment removal model for induction of lasting behavioral and physiological responses to loss. Biology of Loss in Females antidepressant treatment prevented the symptoms of enrichment removal, suggesting a linkage to biological/emotional processes regulated by this class of drug (Smith et al, 2017)
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