Table 1
Daily administration schedule for the analysis of chronic imipramine treatment.
| ZT1 | ZT13 | |
|---|---|---|
| Control | Saline | Saline |
| Morning (imipramine at ZT1) | Imipramine | Saline |
| Evening (imipramine at ZT13) | Saline | Imipramine |

Figure 1
Imipramine exerts dose-dependent antidepressant actions in rats. The rats received imipramine intraperitoneally, after which they were subjected to the forced swim test. Each column represents the mean ± standard error of the mean (SEM) (n = 6 – 8). *p < 0.05, **p < 0.01 vs. control by Williams test.

Figure 2
Acute imipramine treatment produces dosing time-dependent effects in the forced swim test (FST). The rats were administered imipramine at ZT1 (A) or ZT13 (B). One hour after imipramine administration, the rats were subjected to the FST. Each column represents the mean ± standard error of the mean (SEM) (n = 10 – 13). *p < 0.05, **p < 0.01 by Student’s t-test.

Figure 3
Dosing time affects the plasma levels of imipramine and desipramine following acute imipramine treatment. Imipramine (30 mg/kg) was administered at ZT1 or ZT13, and the plasma concentrations of imipramine and desipramine were measured 1 hour later. Each column represents the mean ± standard error of the mean (SEM) (n = 3). *p < 0.05 by 2-way analysis of variance (ANOVA).

Figure 4
Chronic imipramine treatment produces dosing time-dependent effects in the forced swim test (FST). The rats were administered imipramine at ZT1 or ZT13 for 2 weeks, and then subjected to the FST. The effects of chronic imipramine treatment at 10 mg/kg (A) and 30 mg/kg (B) are shown. Each column represents the mean ± standard error of the mean (SEM) (n = 8 – 18). *p < 0.05, **p < 0.01 by Tukey’s test.

Figure 5
Chronic imipramine treatment alters the protein level of adrenergic receptors. Imipramine (30 mg/kg) was chronically administered at ZT1 or ZT13, and the protein levels of α1AR and α2AR were analyzed with western blotting. The levels of α1AR (A, B) and α2AR (C, D) in the prefrontal cortex (PFC) (A, C) and hippocampus (B, D) are shown. Each column shows the mean ± standard error of the mean (SEM) (n = 4). No statistically significant difference was detected between groups by Tukey’s test.
