Reward and motivation deficits are prominent symptoms in many mood disorders, including depression. Similar reward and effort-related choice behavioral tasks can be used to study aspects of motivation in both rodents and humans. Chronic stress can precipitate mood disorders in humans and maladaptive reward and motivation behaviors in male rodents. However, while depression is more prevalent in women, there is relatively little known about whether chronic stress elicits maladaptive behaviors in female rodents in effort-related motivated tasks and whether there are any behavioral sex differences. Chronic nondiscriminatory social defeat stress (CNSDS) is a variation of chronic social defeat stress that is effective in both male and female mice. We hypothesized that CNSDS would reduce effort-related motivated and reward behaviors, including reducing sensitivity to a devalued outcome, reducing breakpoint in progressive ratio, and shifting effort-related choice behavior. Separate cohorts of adult male and female C57BL/6 J mice were divided into Control or CNSDS groups, exposed to the 10-day CNSDS paradigm, and then trained and tested in instrumental reward or effort-related behaviors. CNSDS reduced motivation to lever press in progressive ratio and shifted effort-related choice behavior from a high reward to a more easily attainable low reward in both sexes. CNSDS caused more nuanced impairments in outcome devaluation. Taken together, CNSDS induces maladaptive shifts in effort-related choice and reduces motivated lever pressing in both sexes.

Corticotropin-releasing factor (CRF) in the anterior bed nucleus of the stria terminalis (aBNST) is associated with chronic stress and avoidance behavior. However, CRF+ BNST neurons project to reward- and motivation-related brain regions, suggesting a potential role in motivated behavior. We used chemogenetics to selectively activate CRF+ aBNST neurons in male and female CRF-ires-Cre mice during an effort-related choice task and a concurrent choice task. In both tasks, mice were given the option either to exert effort for high value rewards or to choose freely available low value rewards. Acute chemogenetic activation of CRF+ aBNST neurons reduced barrier climbing for a high value reward in the effort-related choice task in both males and females. Furthermore, acute activation of CRF+ aBNST neurons also reduced effortful lever pressing in high-performing males in the concurrent choice task. These data suggest a novel role for CRF+ aBNST neurons in effort-based decision and motivated behavior.

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