Figure 1
From: Adult hippocampal neuroplasticity triggers susceptibility to recurrent depression
Anhedonic- and anxiety-like behaviors induced by recurrent stress exposure are prevented by imipramine treatment, but not fluoxetine. (a) Schematic representation of the experimental timeline used, including behavioral assessments throughout the protocol and the respective treatments. (b–d) Longitudinal assessment of anhedonic-like behavior by the SPT, revealed an increased susceptibility after re-exposure to stress driven by fluoxetine. (e) Assessment of behavioral despair, at the end of the experimental protocol, by the FST test revealed that recurrent stress exposure induced a significant increase of immobility time, only prevented in animals treated with imipramine. (f–h) Anxiety-like behavior was continuously tested throughout the experimental protocol, at week 6 by the EPM (f) and the NSF at weeks 10 (g) and 16 (h), evidencing the efficacy of imipramine in preventing anxiety-like behavior after stress re-exposure, contrarily to fluoxetine. (i) Non-treated and particularly, fluoxetine-treated animals, subjected to repeated uCMS exposure presented elevated corticosterone levels in the serum. Basal corticosterone levels were measured in the serum of rats collected between 0800 and 0900 at the end of the protocol. See also Supplementary Figures 1 and 2. *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). Data are represented as mean±s.e.m. #P⩽0.05, **, ##P⩽0.01, ***, ###, ‡‡‡P⩽0.001; n=6–8 animals per group. uCMS, unpredictable chronic mild stress protocol (uCMS*, slightly modified version. See Supplementary Information). AD, antidepressant; CTRL, non-stressed animals; EPM, elevated-plus maze; FLX, animals repeatedly exposed to uCMS and treated with fluoxetine; FST, forced-swimming test; IMIP, animals repeatedly exposed to uCMS and treated with imipramine; MWM, Morris water maze; NOR, novel object recognition; NSF, novelty-suppressed feeding; SAL, animals repeatedly exposed to uCMS and non-treated; SDT, sweet-drive test; SPT, sucrose preference test; TP, time point.
