Social isolation influences depression- and anxiety-related disorders and cardiac function. Oxytocin may mediate these conditions through interactions with social behavior, emotion, and cardiovascular function, via central and/or peripheral mechanisms. The present study investigated the influence of oxytocin antagonism using L-368,899, a selective oxytocin receptor antagonist that crosses the blood-brain barrier, on depression- and anxiety-related behaviors and heart rate in prairie voles. This rodent species has translational value for investigating interactions of social stress, behavior, cardiac responses, and oxytocin function. Adult female prairie voles were socially isolated or co-housed with a sibling for 4 weeks. A subset of animals in each housing condition was subjected to 4 sessions of acute L-368,899 (20 mg/kg, ip) or saline administration followed by a depression- or anxiety-related behavioral assessment. A subset of co-housed animals was evaluated for cardiac function following acute administration of L-368,899 (20 mg/kg, ip) and during behavioral assessments. Social isolation (vs. co-housing) increased depression- and anxiety-related behaviors. In isolated animals, L-368,899 (vs. vehicle) did not influence anxiety-related behaviors but exacerbated depression-related behaviors. In co-housed animals, L-368,899 exacerbated depression-related behaviors and increased heart rate at baseline and during behavioral tests. Social isolation produces emotion-related behaviors in prairie voles; central and/or peripheral oxytocin antagonism exacerbates these behavioral signs. Oxytocin antagonism induces depression-relevant behaviors and increases basal and stressor-reactive heart rate in co-housed prairie voles, similar to the consequences of social isolation demonstrated in this model. These results provide translational value for humans who experience behavioral and cardiac consequences of loneliness or social stress.

Caregiving by nonparents (alloparenting) and fathers is a defining aspect of human social behavior, yet this phenomenon is rare among mammals. Male prairie voles (Microtus ochrogaster) spontaneously exhibit high levels of alloparental care, even in the absence of reproductive experience. In previous studies, exposure to a pup was selectively associated with increased activity in oxytocin and vasopressin neurons along with decreased plasma corticosterone. In the present study, physiological, pharmacological and neuroanatomical methods were used to explore the autonomic and behavioral consequences of exposing male prairie voles to a pup. Reproductively naïve, adult male prairie voles were implanted with radiotransmitters used for recording ECG, temperature and activity. Males responded with a sustained increase in heart-rate during pup exposure. This prolonged increase in heart rate was not explained by novelty, locomotion or thermoregulation. Although heart rate was elevated during pup exposure, respiratory sinus arrhythmia (RSA) did not differ between these males and males exposed to control stimuli indicating that vagal inhibition of the heart was maintained. Blockade of beta-adrenergic receptors with atenolol abolished the pup-induced heart rate increase, implicating sympathetic activity in the pup-induced increase in heart rate. Blockade of vagal input to the heart delayed the males' approach to the pup. Increased activity in brainstem autonomic regulatory nuclei was also observed in males exposed to pups. Together, these findings suggest that exposure to a pup activates both vagal and sympathetic systems. This unique physiological state (i.e. increased sympathetic excitation of the heart, while maintaining some vagal cardiac tone) associated with male caregiving behavior may allow males to both nurture and protect infants.