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Depression-Like Behavior and Stressor-Induced Neuroendocrine Activation in Female Prairie Voles Exposed to Chronic Social Isolation

From the Department of Psychiatry and Brain-Body Center, University of Illinois at Chicago, Chicago, IL.

Address correspondence and reprint requests to Angela J. Grippo, PhD, Department of Psychiatry, University of Illinois at Chicago, 1601 W. Taylor St. (MC 912), Chicago, IL 60612. E-mail: agrippo{at}psych.uic.edu

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.

Key Words: affective disorders • corticotropin-releasing factor • hypothalamic-pituitary-adrenal axis • oxytocin • paraventricular nucleus • stress

Abbreviations: ACTH = Adrenocorticotropic hormone; ANOVA = analysis of variance; AVP = arginine vasopressin; CRF = corticotropin releasing factor; DAB = diaminobenzadine; HPA = hypothalamic-pituitary-adrenal; KPBS = potassium phosphate buffered saline; PVN = paraventricular nucleus; SEM = standard error of the mean.

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