Article Figures & Data
Figures
- Figure 1.
The effects of CMS on anhedonia-like behavior. Rats were exposed to CMS for 14, 21, and 35 d (n = 48/group) or handled as control (n = 12). Sucrose preference test was conducted 1 d after the end of each stress procedure. A, Time course of changes in sucrose preference after 14, 21, or 35 d of CMS. Rats exposed to CMS were classified into two phenotypes: susceptible (CMS-S) and resilient (CMS-R) to anhedonia, based on a criterion of 70% preference for sucrose. B, The proportion of anhedonia-susceptible rats after 14, 21, or 35 d of CMS. C–E, Sucrose preference in rats after 14 d (n = CMS-S 22; CMS-R 26), 21 d (n = CMS-S 14; CMS-R 34), or 35 d of CMS (n = CMS-S 35; CMS-R 13). All data are presented as the mean ± SEM; **p < 0.01 compared with control group, &p < 0.05 compared with 14 d CMS group and ##p < 0.01 compared with CMS-S group; one-way ANOVA followed by Tukey’s post hoc test.
- Figure 2.
The effects of CMS on the levels of BDNF, synapsin-1, and PSD-95, as well as spine number in the PFC. Rats exposed to CMS for 14, 21, or 35 d were divided into CMS-S and CMS-R groups based on their sucrose preference. A, C, E, Quantification of protein levels and representative Western blot images of BDNF, synapsin-1, and PSD-95 in the PFC in control, CMS-S, and CMS-R rats after14, 21, or 35 d of CMS. The results were normalized to the level of β-actin in each sample (n = 6/group). B, D, F, Representative photomicrographs for Golgi staining and the number of spines in the PFC in control, CMS-S, and CMS-R rats after 14, 21, or 35 d of CMS (n = 3 neurons/rat, 4 rats/group). Scale bar = 10 μm. All data are presented as the mean ± SEM; *p < 0.05, **p < 0.01 compared with control group and #p < 0.05, ##p < 0.01 compared with CMS-S group; one-way ANOVA followed by Tukey’s post hoc test.
- Figure 3.
The effects of CMS on the basal and evoked glutamate release in the PFC. Rats exposed to CMS for 14, 21, or 35 d were divided into CMS-S and CMS-R groups based on their preference for sucrose. A–C, The basal and depolarization-evoked glutamate release in the PFC in control, CMS-S, and CMS-R rats after 14, 21, or 35 d of CMS (n = 12/group). All data are presented as the mean ± SEM; *p < 0.05, **p < 0.01 compared with control group and #p < 0.05, ##p < 0.01 compared with CMS-S group; one-way ANOVA followed by Tukey’s post hoc test.
- Figure 4.
The effects of prolonged CMS on anhedonia-like behavior, levels of BDNF and synaptic proteins, spine density, and glutamate release in the PFC in former anhedonia-susceptible rats. A, Schedule of experiment. Rats were exposed to CMS for 21 d, and those susceptible to anhedonia were picked out by SPT on day 15. A second round of SPT was conducted on day 22 to reexamine their susceptibility to anhedonia. Rats were re-divided into CMS-S and CMS-R groups based on a 70% preference for sucrose as the criterion. B, The proportion of anhedonia-susceptible rats after 21 d of CMS. C, Sucrose preference in rats after 21 d of CMS (n = control 12; CMS-S 14; CMS-R 17). D, Quantification of protein levels and representative Western blot images of BDNF, synapsin-1, and PSD-95 in the PFC in rats after 21 d of CMS. The results were normalized to the level of β-actin in each sample (n = 6/group). E, Representative photomicrographs for Golgi staining and the number of spines in the PFC in rats after 21 d of CMS (n = 3 neurons/rat, 4 rats/group). Scale bar = 10 μm. F, The basal and depolarization-evoked glutamate release in the PFC in rats after 21 d of CMS (n = 12/group). All data are presented as the mean ± SEM; *p < 0.05, **p < 0.01 compared with control group and #p < 0.05, ##p < 0.01 compared with CMS-S group; one-way ANOVA followed by Tukey’s post hoc test.
- Figure 5.
The effects of ketamine on anhedonia-like behavior, levels of BDNF and synaptic proteins, spine density, and glutamate release in the PFC in rats after 14 d of CMS. A, Schedule of experiment. Rats were exposed to CMS for 14 d, and those susceptible to anhedonia were picked out by SPT on day 15. The anhedonia-susceptible rats were injected with saline or ketamine (10 mg/kg) on day 16, and their anhedonia-like behaviors were examined by SPT on day 17. B, Sucrose preference in rats after 14 d of CMS and ketamine treatment (n = 12/group). C, Quantification of protein levels and representative western blot images of BDNF, synapsin-1, and PSD-95 in the PFC in rats after 14 d of CMS and ketamine treatment. The results were normalized to the level of β-actin in each sample (n = 6/group). D, Representative photomicrographs for Golgi staining and the number of spines in the PFC in rats after 14 d of CMS and ketamine treatment (n = 3 neurons/rat, 4 rats/group). Scale bar = 10 μm. E, The basal and depolarization-evoked glutamate release in the PFC in rats after 14 d of CMS and ketamine treatment (n = 12/group). All data are presented as the mean ± SEM; *p < 0.05, **p < 0.01 compared with control group and #p < 0.05, ##p < 0.01 compared with CMS-S + vehicle group; one-way ANOVA followed by Tukey’s post hoc test.
- Figure 6.
The effects of ketamine on anhedonia-like behavior, levels of BDNF and synaptic proteins, spine density, and glutamate release in the PFC in rats after 35 d of CMS. A, Schedule of experiment. Rats were exposed to CMS for 35 d, and those susceptible to anhedonia were picked out by SPT on day 36. The anhedonia-susceptible rats were injected with saline or ketamine (10 mg/kg) on day 37, and their anhedonia-like behaviors were examined by SPT on day 38. B, Sucrose preference in rats after 35 d of CMS and ketamine treatment (n = 12/group). C, Quantification of protein levels and representative western blot images of BDNF, synapsin-1, and PSD-95 in the PFC in rats after 35 d of CMS and ketamine treatment. The results were normalized to the level of β-actin in each sample (n = 6/group). D, Representative photomicrographs for Golgi staining and the number of spines in the PFC in rats after 35 d of CMS and ketamine treatment (n = 3 neurons/rat, 4 rats/group). Scale bar = 10 μm. E, The basal and depolarization-evoked glutamate release in the PFC in rats after 35 d of CMS and ketamine treatment (n = 12/group) All data are presented as the mean ± SEM; *p < 0.05, **p < 0.01 compared with control group and #p < 0.05, ##p < 0.01 compared with CMS-S + vehicle group; one-way ANOVA followed by Tukey’s post hoc test.
- Figure 7.
Time course of the effects of CMS on BDNF levels and glutamate release in the PFC. BDNF levels in the PFC are decreased in rats that are susceptible to CMS-induced anhedonia. Prefrontal glutamate release in CMS-susceptible rats is enhanced after 14 d of CMS, but it becomes reduced after 35 d of CMS. Anhedonia-like behavior in CMS-susceptible rats can spontaneously decrease, accompanied by restoration of BDNF levels and glutamate release, on day 21 of CMS. In contrast, BDNF levels and glutamate release in the PFC remain normal in rats that are resilient to CMS-induced anhedonia.
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