Fig 1.
Upon arrival at the facility, mice were subjected to either unstressed, mild stress, or unpredictable chronic stress (UCS) conditions, where UCS daily hassles began the next day. Following this period of stress or no stress, all mice received a single injection (Day 0) of either vehicle (0.9% saline, i.p.), 10 mg/kg ketamine, or 30 mg/kg ketamine. 24 hours later (Day 1), mice were given a forced swim test (FST1), followed by a second FST on Day 7 and an open field test (OFT) on Day 8. In additional control experiments, another cohort of mice was injected on Day 0, and given an OFT on Day 1 and on Day 7.
Fig 2.
Chronic mild stress and ketamine interact in the mouse forced swim test.
Behavior 24 hours post-ketamine was automatically scored in EthoVision and parsed into: A, climbing (highly mobile) behavior; B, swimming (intermediately mobile behavior); C, immobile behavior. Swimming behavior in particular revealed differential effects of ketamine according to stress status. Additional swim tests were carried out 7 days post-ketamine: D, climbing behavior; E, swimming behavior; F, immobile behavior. Results trended in the same direction as at the 24 hour time point. Error bars: ± standard error of mean (SEM). Significance indicators for post-hoc tests (horizontal brackets) or two-way ANOVAs (centered over each graph) marked by *p < 0.05, **p < 0.01.
Fig 3.
Chronic mild stress but not ketamine modulates the open field test.
Behavior (8 days post-injection) was automatically scored in EthoVision and parsed into: A, total distance traveled; B, center square entries; C, percent center square time. There was a main effect of stress, indicating modulation of total distance traveled (p < 0.01), as well as percent center square time (p < 0.01), with a trend for center square entries (p = 0.078). Error bars: ± SEM. Two-way ANOVA ** p < 0.01.
Fig 4.
Chronic mild stress disrupts the relationship between FST swimming (mobile) behavior and OFT distance traveled.
Each point in each graph represents FST swimming behavior (7 days post-injection, abscissa) versus OFT distance traveled (8 days post-injection, ordinate) for an individual mouse. The correlation coefficient (r) and corresponding p value are shown on each graph. While FST 7 days post-injection swimming and OFT Day 8 distance traveled are correlated in two of three unstressed cohorts, none of the stress cohorts show significant correlation between these metrics.
Table 1.
Correlations between FST and OFT behavior.