Oxytocin-dependent reorganization of social vs. food motivational hierarchy and corticostriatal neural activity by social isolation in rats

Social interactions are crucial for the survival and well-being of mammalian individuals. The social homeostasis theory proposes that mammals actively regulate social interactions to maintain an optimal set-point, similar to feeding behavior. Yet, how the social homeostatic drive interacts with competing fundamental needs remains unclear. Moreover, the brain mechanisms underlying social homeostasis are still elusive. A potential such mechanism is oxytocin, a hypothalamic neuropeptide regulating both social and feeding behaviors. We used chronic electrophysiological recordings from behaving rats to analyze local field potential (LFP) signals simultaneously recorded from a network of brain areas associated with reward, motivation, and decision making, while the animals chose between food and social investigation. These experiments were conducted across multiple conditions of social and food deprivation to explore the interplay between the competing needs for food consumption and social interaction. We found that group-housed rats shifted preference toward food under 24-hour food deprivation, whereas socially isolated rats maintained social preference despite equivalent metabolic need. Remarkably, isolation-induced social bias persisted even after one week of re-grouping the animals, indicating long-term reorganization of motivational priorities due to social isolation. LFP recordings revealed that isolated rats exhibited elevated theta power and enhanced network coherence, compared to group-housed rats while making a choice between food to social investigation, regardless of their metabolic state. Canonical correlation analysis demonstrated that metabolic state and housing condition are encoded in orthogonal neural dimensions, suggesting that social isolation creates distinct neural signatures rather than disrupting metabolic state encoding. Systemic administration of an oxytocin receptor antagonist restored balanced social-food investigation in isolated rats and selectively suppressed theta oscillations in specific corticostriatal regions during social investigation. These findings establish oxytocin-regulated theta oscillations as a neural substrate through which social experience reorganizes motivational hierarchies. Our results thus demonstrate that social needs can override metabolic drives through oxytocin-dependent modulation of corticostriatal network dynamics.