Chronic non-discriminatory social defeat stress reduces effort-related motivated behaviors in male and female mice

Andrew Dieterich,Benjamin Adam Samuels,Tonia Liu

doi:10.1038/s41398-021-01250-9

Andrew Dieterich, Benjamin Adam Samuels + Show 1 more

Open Access

https://doi.org/10.1038/s41398-021-01250-9

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Abstract

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.

Highlights

Major depressive disorder (MDD) is a prevalent and costly psychiatric disorder that affects more than 10% of the population and can be precipitated by chronic exposure to stressors[1,2,3,4]
CD-1 aggressions were averaged for each mouse, and similar to our original Chronic nondiscriminatory social defeat stress (CNSDS) report[27], an independent samples t-test indicated that CNSDS males were aggressed more frequently than females (t(38) = 13.26, p < 0.0001) (Supplemental Fig. 3B)
Our understanding of whether there are sex differences in how chronic stress affects behavior has been hampered by a lack of chronic stress paradigms that are effective in both male and female mice

Summary

Introduction

Major depressive disorder (MDD) is a prevalent and costly psychiatric disorder that affects more than 10% of the population and can be precipitated by chronic exposure to stressors[1,2,3,4]. Half of those diagnosed with MDD suffer from anhedonia, and reward processing deficits occur in many other disorders including schizophrenia and substance abuse disorder[5,6]. Studying individual behavioral components of reward function in rodents exposed to chronic stress should help improve our understanding of the etiology of psychiatric disorders. In an effort-expenditure for rewards task (EEfRT) where participants have the option between low effort/low monetary reward and high

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