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

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.

Chemogenetic activation of corticotropin-releasing factor-expressing neurons in the anterior bed nucleus of the stria terminalis reduces effortful motivation behaviors

“…Chronic stress leads to sustained increases in activity of CRF+ aBNST neurons [16, 19, 21–23] and impairs effortful motivation behavior [3, 5]. Therefore, we wondered whether chemogenetic activation of aBNST CRF neurons would be sufficient to mimic the effects of chronic stress on effort-related choice.…”

“…Having to climb this barrier increases the effort requirements for the higher value reward while the lower value reward remains freely available [41, 42]. Both female and male mice exposed to chronic stress shift to choosing the LR arm at shorter barrier heights than control mice [3, 5]. All mice were administered i.p.…”

“…Chemogenetic activation of CRF+ aBNST neurons in both female and male mice decreases willingness to exert effort for a high value reward in effort-related choice Chronic stress leads to sustained increases in activity of CRF+ aBNST neurons [16,19,[21][22][23] and impairs effortful motivation behavior [3,5]. Therefore, we wondered whether chemogenetic activation of aBNST CRF neurons would be sufficient to mimic the effects of chronic stress on effort-related choice.…”

Reactivation of early-life stress-sensitive neuronal ensembles contributes to lifelong stress hypersensitivity

“…Both male and female mice were exposed to chronic non-discriminatory social defeat stress (CNSDS) (Dieterich et al, 2021; Yohn et al, 2019), a modified version of chronic social defeat stress (Berton et al, 2006) for simultaneous social stress of male and female mice. Briefly, beginning at age P60, CNSDS-assigned mice were subject to 10 days of daily social defeat by a Swiss Webster retired breeder (“aggressor;” Taconic) in a standard rat cage filled with corn cob bedding.…”

Chronic stress-induced synaptic changes to corticotropin-releasing factor-signaling in the bed nucleus of the stria terminalis

“…In CNSDS, aggressor mice are driven to attack both sexes when both a male and a female mouse are simultaneously placed into their home cage ( Yohn et al, 2019 ). Importantly, CNSDS results in susceptible and resilient phenotypes in both sexes, and increases avoidance while decreasing reward behaviors ( Yohn et al, 2019 ; Dieterich et al, 2021 ).…”