Depression-like behavior and stressor-induced neuroendocrine activation in female prairie voles exposed to chronic social isolation

Abstract

Objective: To assess whether the responses of prairie voles to social stressors play a mechanistic role in the behavioral and physiological changes associated with affective disorders such as depression, as suggested in previous studies. Prairie voles (Microtus ochrogaster) are socially monogamous rodents that share features of social behavior with humans; therefore, they may serve as useful models for examining social behavioral regulations and physiological responses related to depression. In this study, we hypothesized that social isolation in female prairie voles would induce depression-relevant behaviors and alter their neuroendocrine responses to an acute social stressor.

Methods: Twenty adult female prairie voles were exposed to either 60 days of social isolation or paired (control) housing. They were tested and observed for a depression-like behavior (anhedonia). The levels of corticotropin-releasing factor- and oxytocin-immunoreactive cells in the paraventricular nucleus of the hypothalamus and circulating levels of hormones and peptide were measured in response to an acute social stressor (resident-intruder test).

Results: Chronic social isolation produced anhedonia, measured by reduced sucrose intake and sucrose preference relative to the control animals. Compared with the paired animals, the isolated prairie voles displayed increased plasma hormone and peptide levels (oxytocin, arginine vasopressin, and corticosterone) after a 5-minute resident-intruder test, mirrored by an increased number of oxytocin- and corticotropin-releasing factor-immunoreactive cells in the hypothalamic paraventricular nucleus.

Conclusions: These findings suggest that isolation in a socially monogamous rodent model induces both behavioral and neuroendocrine changes that are relevant to depression. These results may provide insight into the mechanisms that underlie the development and/or maintenance of depressive disorders in humans.

Figure 1

Mean (+ SEM) absolute water and sucrose intake (Panel A) and mean sucrose preference (Panel B) in paired and isolated prairie voles following 50 days of social isolation. *P < 0.05 versus respective paired value.

Figure 2

Mean (+ SEM) number of aggressive episodes during the resident-intruder test (Panel A) and number of agitated behaviors following the resident-intruder test (Panel B) in paired and isolated groups. Note the scale differences in Panels A and B. *P < 0.05 vs. paired value.

Figure 3

Mean (+ SEM) circulating levels of oxytocin (Panel A), AVP (Panel B), ACTH (Panel C), and corticosterone (Panel D) in paired and isolated prairie voles at 10 minutes following a 5-minute resident-intruder test. Note the scale differences among the 4 panels *P < 0.05 versus paired value.

Figure 4

Brain sections (40 μm) showing oxytocin- (Panels A and B) and CRF-immunoreactivity (Panels C and D) in representative paired (Panels A and C) and isolated (Panels B and D) prairie voles in the hypothalamic PVN. Pictures are shown at 100× magnification. Scale bars = 100 μm. Stained fibers were excluded from analysis.

Figure 5

Mean (+ SEM) number of oxytocin- (Panel A) and CRF-immunoreactive (Panel B) cells in the hypothalamic PVN in paired and isolated prairie voles. Note the scale differences in Panels A and B. *P < 0.05 versus paired value. Stained fibers were excluded from analysis.