Chronic mild stress in submissive mice: Marked polydipsia and social avoidance without hedonic deficit in the sucrose preference test

•Selectively bred Sub mice are highly sensitive to the anxiogenic effects of CMS.•Stressed Sub mice, but not Wt, displayed impaired social exploration.•Stressed mice displayed polydipsia, without altered sucrose consumption.•The EPM and Three Chamber tests may be valuable complementary measures of CMS effects.

In the Chronic Mild Stress (CMS) protocol, rodents are exposed to unpredictable stressors to induce anxiety-like behavior and hedonic deficit in the Sucrose Preference test (SPT). Since CMS-induced anxiety- and anhedonic-like behavior may depend upon individual vulnerability to stress, we hypothesized that selectively bred Submissive (Sub) mice would exhibit heightened anxiety- and anhedonic-like behavior, in response to CMS exposure. We anticipated that the testing of Sub mice alongside their Wt counterparts in a battery of behavioral assays would identify parameters most sensitive to CMS effects. To test these assumptions, Sub mice and their outbred Sabra (Wt) counterparts underwent a five-week CMS-SPT regimen.CMS exposure led to reduced preference for sucrose (sucrose-sweetened water as percent of total intake) among both mouse strains (p < 0.01 Wt; p < 0.05 Sub). However, this effect was attributed to CMS-induced polydipsia, indicated by mice's increased water consumption, (p < 0.01 Wt and Sub), without changes in sucrose intake. Furthermore, CMS-exposed Sub mice, but not Wt, demonstrated impaired social exploration in the Three Chamber test (p < 0.05) and anxiety-like effects in the Elevated Plus Maze (p < 0.05). Moreover, in a separate experiment, social isolation alone was sufficient to induce polydipsia in Sub mice, without affecting Wt mice's drinking behavior. The present findings suggest that the EPM and Three Chamber tests may be valuable complementary measures of CMS effects, alongside the Sucrose Preference test, and introduce the Sub mouse strain for use in study of susceptibility to stress.