Social relationships are essential for many fundamental aspects of life and influence behavior and physiology.Disruption to social bonds can be detrimental to mental and physical health.Male prairie voles form enduring social bonds with their female partners,providing a unique opportunity to evaluate the impact of partner loss.In this study,males were paired with a novel female for 24 h,then evaluated for partner preference (PP) formation.Of those that displayed a PP,half were separated from their partner for 4 wk.Partner loss significantly increased anxiety-like behaviors in the elevated plus-maze and light-dark box tests and marginally increased depressive-like behaviors in the forced swim test.Partner loss also eliminated bond-related behaviors in a time-dependent manner.While PP was observed after 2 wk of partner loss,both PP and intruder-directed behaviors were eliminated after 4 wk partner loss.Oxytocin-immunoreactivity (-ir) ,vasopressin-ir,and corticotrophin-releasing hormone-ir density were all decreased in the paraventricular nucleus of separated males.Oxytocin-ir was decreased in the supraoptic nucleus,but dopamine-ir was not affected.Body weight gain and plasma corticosterone concentrations were elevated throughout the 4 wk of partner loss,with no effects for plasma oxytocin or vasopressin.These data suggest that partner loss in male prairie voles elicits depression-like and anxiety-like behaviors It also disrupts bond-related behaviors,in a time-dependent manner,as well as neuropeptide systems that regulate social behavior.Thus,partner loss in male prairie voles may provide a model to better understand the behavior,pathology,and neurobiology underlying partner loss and grief.