Evaluation of Antidepressive-like Behaviours and Oxidative Stress Parameters in Mice Receiving Imipramine-Zinc Complex Compound

Abstract

The study aimed to evaluate the antidepressant-like effects of an imipramine-zinc (IMI-Zn) complex compound on mice and assess the level of oxidative stress parameters. The research also investigated whether the IMI-Zn complex showed superior antidepressant activity compared to individual treatments of both compounds at effective doses and their joint administration at subtherapeutic doses. The study was conducted on mice. Forced swim (FST), tail suspension (TST), and locomotor activity tests were used for behavioral studies. The results demonstrated the IMI-Zn complex's dose-dependent antidepressant potential when orally administered to mice. Its efficacy was similar to the separate administration of therapeutic doses of imipramine (IMI) and zinc (Zn) and their joint administration at subtherapeutic doses. Moreover, subjecting mice to acute stress did not significantly affect the activity of on glutathione peroxidase (GPX), glutathione reductase (GR), and total antioxidant status (TAS), possibly due to the short exposure time to the stress stimulus. By developing the IMI-Zn complex, it might be possible to simplify the treatment approach, potentially improving patient compliance by combining the therapeutic effects of both IMI and Zn within a single compound, thus addressing one of the contributing factors to non-compliance in depression therapy. The IMI-Zn complex could be a valuable strategy to optimize therapeutic outcomes and balance efficacy and tolerability.

Keywords: antidepressant-like activity; environmental stress; glutathione peroxidase; glutathione reductase; imipramine-zinc complex; mice; oxidative stress; total antioxidant status.

Figure 1

Effect of IMI-Zn complex administration on mice behaviors in the FST (A) and TST (B). IMI-Zn complex (5–100 mg/kg) and IMI (90 mg/kg) were administered orally 60 min before behavioral testing. Mice from the control group received 0.9% NaCl, whereas IMI was a positive control. The values represent the mean ± S.E.M. (n = 10 mice/group). * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001 vs. 0.9% NaCl-treated group (one-way ANOVA followed by Dunnett’s post-hoc test).

Figure 2

Comparison of the antidepressant-like effect of IMI-Zn complex and IMI, Zn and their joint administration on animal behaviors in the FST (A) and TST (B) in mice. IMI-Zn complex (20 mg/kg), IMI (60 and 90 mg/kg), and Zn (40 and 60 mg/kg) were administered orally 60 min before behavioral testing. Mice from the control group received 0.9% NaCl. The values represent the mean ± S.E.M. (n = 10 mice/group). * p < 0.05, ** p < 0.01, **** p < 0.0001 vs. 0.9% NaCl-treated group, not statistically significant (ns) p > 0.05 vs. relevant treated group (one-way ANOVA followed by Tukey’s post-hoc test).

Scheme 1

Research scheme. Studies were divided into three steps: I. Dose-effect studies; II. Comparison studies, and III. Experiments done on naïve mice. Different cohorts of mice were used for all three steps. Mice used in steps I-II were further divided into two groups: one subjected to FST and the second to locomotor activity and TST. After the tests, mice were decapitated, and blood was collected for biochemical studies. III. Naïve mice were not taken for any tests. They were decapitated, and blood was collected for biochemical studies.