Fig. 1. Chronic antidepressant treatments produced anti-depressive-like effects, but induced anxiety-like behavior. (A) Experimental design for chronic administration of saline (Veh), imipramine (IMI) or fluoxetine (FLX) daily for 14 consecutive days and more, followed by behavioral tests. Behavioral tests were carried out in the following order: novelty suppressed feeding test (NSF), forced swim test (FST), and sociability test in the IMI treatment groups, and elevated plus maze (EPM), tail suspension test (TST), and open field test (OFT) in the FLX treatment groups. (B~F) Mice treated with chronic IMI showed decreased immobility in the FST (B). In the sociability test, IMI-treated mice spent a similar amount of time as that of control mice in the interaction zone (C), but significantly more time in the corner zone (D), a behavioral sign of anxiety. In the novelty suppressed feeding (NSF) test, IMI-treated mice showed increased latency to eating a food pellet in the center (E), as well as decreased food consumption examined for 5 min immediately after administrating the NSF test (F). (G~J) Mice treated with chronic FLX showed decreased immobility in the TST (G). In the open field test, FLX-treated mice exhibited decreased locomotor activity (H). In the EPM test, FLX-treated mice had decreased entries to the open arms (I) and spent less time in the open arms (J). Data are presented as the mean±SEM (n=8 animals for FST; n=12~14 animals for sociability test; n=6~8 animals for NSF; n=7~8 animals for TST; n=7 animals for OFT; n=6~8 animals for EPM). * and **denote differences between the two groups at p<0.05 and p<0.01. Student's t-test was used.
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