How food reward value induces positive memories to alleviate anxiety-related behavior in mice

Anxiety and stress are emerging as major psychological problems in modern society, and treatments that strengthen positive memories/emotions offer promising new avenues. We investigated whether the palatability of food influences the formation of reward-associated memories that can alleviate anxiety-related behaviors in mice. Three experiments combined the elevated plus maze (EPM) and runway task. In the first experiment, mice were trained with standard food or given neutral training and later tested to determine whether food reward-induced memories enhance open-arm exploration, approach frequency, locomotor level, and latency of reaching the previously rewarded arm. Mice that had received food training subsequently showed stronger preference for the previously rewarded open arm and exhibited fewer anxiety-related behaviors than those without food rewards. The second experiment compared the motivational properties of highly palatable (reward value) food with standard food using a straight-runway test that captured running speed, pausing and reversing behavior. Mice facing for high reward value (HRV) food displayed more vigorous and direct approach behavior, confirming its greater incentive value. Building on these findings, the third experiment tested whether reward-associated memories formed with HRV food more effectively alleviate anxiety-related behavior than those formed with standard food. When later evaluated in the EPM without food present, mice trained with HRV food showed greater open-arm exploration and activity. These results indicate significant variations in the attractiveness of different food reward values to mice and that the reward-associated memories formed by these variations significantly influence anxiety behavior. This study contributes to understanding the interaction between food reward values and memory, which inform strategies for anxiety management. • Reward-induced memories formed through food-reward training can alleviate anxiety-related behaviors. • Food rewards are a potent tool for training mice to induce reward memories. • High reward value food training enhanced goal-directed approach behavior. • Modulating reward memory through food reward values affect anxiety-related behavior in mice.