Repeated Social Defeat Stress Induces Individual Differences in Effort-Based Motivation Dissociable from Social Avoidance in Mice

Depression is characterized by motivational disturbances, including reduced hedonic value of rewards (consummatory anhedonia) and altered sensitivity to effort-related costs. Although repeated social defeat stress (RSDS) induces individual differences in social avoidance, its effects on effort-based motivation remain unclear. We developed a wall-climbing-based effort-based decision-making test with minimal cognitive demand to assess cost-benefit decision-making in mice. Mildly food-restricted mice were given a choice between a low-effort/low-reward food pellet and a high-effort/high-reward chocolate reward placed behind a wall of increasing height. At low wall heights, all RSDS-exposed mice preferred the chocolate reward, indicating preserved hedonic value. However, as wall height increased, RSDS-exposed mice segregated into two subgroups: "R-High" mice, which maintained a preference for the high-reward option, and "R-Low" mice, which shifted toward the low-effort option. This shift was not attributable to physical incapacity, as R-Low mice successfully climbed higher walls in an escape context. These subgroups did not differ in social avoidance, sucrose preference, or body weight. Laser microdissection followed by RT-qPCR, performed approximately 30 d after the completion of RSDS, revealed a selective reduction in dopamine D1 receptor (Drd1) mRNA expression in the nucleus accumbens of R-Low mice. In contrast, downregulation of glucocorticoid receptor (Nr3c1) and mineralocorticoid receptor (Nr3c2) was common to both RSDS subgroups. These findings suggest that individual differences in effort-based motivation following RSDS are dissociable from RSDS-induced social avoidance and occur despite preserved consummatory reward preference. Reduced accumbal D1 receptor signaling may contribute, at least in part, to the molecular mechanisms underlying stress-induced motivational deficits.