Figure 2

Evaluation of cognitive function throughout the experimental protocol revealed that imipramine is able to prevent cognitive deficits induced by recurrent stress exposure while fluoxetine specifically prevents alterations in behavior flexibility. (a–c) Continuous assessment of long-term memory using the novel object recognition (NOR) test revealed that recurrent stress induces cognitive deficits, which are also observed in fluoxetine-treated animals but not with imipramine treatment. (d–g) At the end of the protocol, the MWM test was used to evaluate cognitive performances, including working (d) and reference memory (e), reversal learning (f) and working memory by a probe trial (g). *Denotes the effect of uCMS analyzed by Student’s t-test; ^#Denotes the effect of ADs, by comparison of treatment and SAL animals; and ^‡denotes differences between ADs analyzed by one-way analysis of variance (ANOVA). ANOVA repeated measures was used to analyze cognitive learning tasks performance. Data are represented as mean±s.e.m. ^{*, #}P⩽0.05, ^{**, ##, ‡‡}P⩽0.01, ^{***, ###, ‡‡‡}P⩽0.001; n=6–8 animals per group. AD, antidepressant; AUC, area under the curve; CTRL, non-stressed animals; FLX, animals repeatedly exposed to uCMS and treated with fluoxetine; IMIP, animals repeatedly exposed to uCMS and treated with imipramine; MWM, Morris water maze; NOR, novel object recognition; SAL, animals repeatedly exposed to uCMS and non-treated; TP, time point; uCMS, unpredictable chronic mild stress protocol.