Neural and Behavioral Correlates of Individual Variability in Rat Helping Behavior: A Role for Social Affiliation and Oxytocin Receptors.

A prosocial response to others in distress is increasingly recognized as a natural behavior for many social species. While prosocial behavior is more frequently observed toward familiar conspecifics, even within the same social context, some individuals are more prone to help than others. In a rat helping behavior test where animals can release a distressed conspecific trapped inside a restrainer, most rats are motivated and consistently release the trapped rat ("openers"), yet ∼30% do not open the restrainer ("nonopeners"). To characterize the difference between these populations, behavioral and neural markers were compared between opener and nonopener rats in males and females. Openers showed significantly more social affiliative behavior both before and after door opening compared with nonopeners. Oxytocin receptor mRNA levels were higher in the nucleus accumbens (NAc), but not the anterior insula, of openers. Several transcription control pathways were significantly upregulated in openers' NAc. Chemogenetically inhibiting paraventricular oxytocin neurons did not significantly impair helping but reduced sociality measures, indicating that helping does not rely solely on oxytocin signaling. Analysis of brain-wide neural activity based on the immediate-early gene c-Fos in males revealed increased activity in openers in prosocial brain regions compared with nonopeners. These include regions associated with empathy in humans (insula, somatosensory, cingulate, and frontal cortices) and motivation and reward regions such as the NAc. These findings indicate that prosocial behavior may be predicted by affiliative behavior and activity in the prosocial neural network and provide targets for the investigation of causal mechanisms underlying prosocial behavior.