Characterization of male and female rats’ responses to social isolation and unpredictable stress: Motivational and hedonic effects

Stress-related disorders show marked sex differences, yet the interaction between sex and stressor type remains poorly understood. In addition, motivational processes underlying reward-related behavior can be dissociated into hedonic ("liking") and effort-based ("wanting") components, which may be differentially affected by stress. The present study aimed to evaluate how sex and type of stressor modulate anxiety-like behavior, hedonic processing, and motivation. Male and female rats were exposed to either chronic unpredictable stress battery (CUSB) or post-weaning social isolation (PWSI). Behavioral assessment included open field test for anxiety-like behavior, both saccharin preference and free-choice consumption for liking behavior, and progressive ratio paradigms for wanting behavior. We found that females exhibited increased anxiety-like behavior and reduced motivation in effort-based tasks under both stress conditions, while maintaining intact hedonic processing. In contrast, males showed stressor-dependent effects: both CUSB and PWSI induced anhedonia, but only CUSB produced additional anxiety-like behavior and reduced motivation. These findings demonstrate that stress responses are shaped by both sex and stressor type, leading to distinct behavioral profiles. Importantly, our results reveal a dissociation between hedonic and motivational components of reward processing that depends on sex and stress conditions. Overall, this study supports a shift from vulnerability-based interpretations toward a framework of adaptive behavioral strategies and highlights the importance of integrating sex differences and stressor characteristics in preclinical models of stress.