Time-dependent changes in cognitive flexibility performance during intermittent social stress: Relevance for motivation and reward-seeking behavior

Abstract

Repeated exposure to stress produces cognitive impairments that can lead to psychiatric disorders. How and when these cognitive impairments occur during repeated exposure to stress is not well understood. The present study investigates the time course effects of the exposure to intermittent episodes of social stress on cognitive flexibility performance. Male rats were trained to perform a cognitive flexibility (set-shifting) task. Then they were submitted to intermittent social defeat stress, which consisted of exposing animals to social defeat once every three days for ten days (four stress episodes). Set-shifting performance was evaluated before and in between social stress episodes, and up to ten days after the end of the stress protocol. Plasma levels of corticosterone after tail-pinch were also measured after the last set-shifting session. Intermittent exposure to social stress did not impair cognitive flexibility but produced short-and long-term changes in set-shifting performance. After the third social defeat episode, stressed animals required significantly more time to respond to cues (instrumental action) and to poke in the food-trough when no food pellet was delivered. These effects were reversed ten days after stress and suggest a decrease in motivation to pursue rewards. In contrast, stressed animals responded more accurately to light cues that predicted rewards. This effect, which emerged ten days after stress, suggests an increase in the reactivity to salient cues in the long-term. These time-dependent behavioral changes might help to understand the transition from social stress to stress-related disorders including drug abuse.