Fig. 2. Chronic antidepressant treatments impaired the animal's stress-coping ability in regulating anxiety-related behavior, but not in depression-related behavior. (A) Experimental design of chronic administration of saline (Veh), imipramine (IMI) or fluoxetine (FLX), following treatment with restraint for 6 h daily for 3 consecutive days (RST, 6h×3d), and subsequent behavioral tests. Behavioral tests were carried out for more than three independent sets of experimental groups. CON, untreated naïve mice. Behavioral tests were carried out in the order of the EPM test, sociability test, MBT, NSF test, OFT, TST, and rotarod test. (B, C) The percentage of entry numbers to the open arms (B) and the percentage of the time spent in the open arms (C) in the EPM test, among untreated mice (CON), mice treated with chronic IMI or FLX,and mice treated with chronic saline (Veh), IMI or FLX followed by 6h×3d RST. (D, E) The traveled distance of animals in the open field test (D), and the time spent in the center zone of the open field (E), among untreated mice (CON), mice treated with chronic IMI or FLX, and mice treated with chronic Veh, IMI or FLX followed by 6h×3d RST. (F, G) Latency to eating a food pellet in the center of the open field in the novelty suppressed feeding (NSF) test (F), and the amount of food consumption assessed immediately after the NSF test (G), among untreated mice (CON), mice treated with chronic IMI or FLX, and mice treated with chronic Veh, IMI or FLX followed by 6h×3d RST. (H) The number of marbles buried in the marble burying test (MBT), among untreated mice (CON), mice treated with chronic IMI or FLX, and mice treated with chronic Veh, IMI or FLX followed by 6h×3d RST. (I) Immobility time in the tail suspension test, among untreated mice (CON), mice treated with chronic IMI or FLX, and mice treated with chronic Veh, IMI or FLX followed by 6h×3d RST. (J, K) Interaction time with a social target in the interaction zone (J) and the corner zone (K) in the sociability test, among untreated mice (CON), mice treated with chronic IMI or FLX or mice treated with chronic Veh, IMI or FLX followed by 6h×3d RST. (L, M) Performance on the rota-rod rotating at 10 rpm (L) and 15 rpm (M), exhibited by untreated mice (CON), mice treated with chronic IMI, and mice treated with chronic Veh or IMI followed by 6h×3d RST. Data are presented as the mean±SEM (n=4~9 animals for EPM; n=6~9 animals for OFT; n=8~10 animals for NSF; n=9~10 animals for MBT; n=8 animals for TST; n=7~8 animals for sociability test; n=7~8 for rotarod test). * and **denote differences from CON group; # and ##denoted differences from the Veh+RST group; § and §§denoted differences from the IMI group, at p<0.05 and p<0.01, respectively. †denoted difference from the FLX group, at p<0.05. Two-way ANOVA and Newman-Keuls post hoc test was used in statistical analysis.
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