State-dependent reward circuit modulation gates social buffering of stress

Social experiences can profoundly shape emotional regulation and promote resilience to stress. Although the presence of companions is well-known to buffer the impact of stress in humans and rodents1–5, whether and how social interactions restore the disruptions in reward processing commonly produced by stress remains unknown. Here, we developed a reward-based behavioral paradigm to study social buffering. Brief interaction with a familiar, unstressed partner following acute restraint stress restored reward-seeking behavior in both female and male C57BL6/J mice. Our findings indicate that buffering is an active process driven by the stressed individual, rather than a passive outcome of social interaction. Ventral tegmental area (VTA) GABAergic, but not dopaminergic, neurons play a key role in mediating this effect. Critically, temporally precise inhibition of VTA GABA neuron activity is sufficient to convert a non-buffering interaction with a novel partner into a buffering experience, whereas identical inhibition delivered outside of a social context is ineffective. These results reveal a previously unrecognized role for socially elicited VTA GABA neuron activity in gating the response to stress and position the stressed individual’s behavior as a key determinant of resilience. Given the central role of stress-induced reward deficits in psychiatric disorders, these findings have broad implications for understanding resilience and the development of novel therapies.