ABSTRACT
The present study focused on examining the impact of vitamin C (Vit C) administration on the function of memory and the status of oxidative stress (OS) in the hippocampal area of the brain using an unpredictable chronic mild stress (UCMS) model in rats. To this end, 50 male Wistar rats (11-12 weeks of age at the start of the study) were assigned to five groups of six animals, including control, UCMS, UCMS + Vit C 50 mg/Kg, UCMS + Vit C 100 mg/Kg, and UCMS + Vit C 400 mg/Kg. The animals received daily intraperitoneal injections of Vit C at a certain time (9 am) before the initiation of a stressor. UCMS, including a progression of typical stressors, was applied for four weeks. Subsequently, using the passive avoidance (PA) and Morris water maze (MWM) tests were performed to investigate learning and memory. Eventually, hippocampal tissues were evaluated in terms of OS criteria. The results revealed that the latency to enter the dark chamber (P < 0. 01 and P < 0.05, PA test) and the time spent in the target quadrant (P < 0.0001, MWM test) were shorter in the UCMS group, while latency to discover the platform was longer (P < 0.05 and P < 0.001, MWM test) compared to the control group. However, UCMS decreased the content of thiol (P < 0.0001), as well as the activities of catalase (P < 0.0001) and superoxide dismutase (P < 0.0001), whereas the concentration of malondialdehyde (P < 0.01) increased in the hippocampal region of the brain in comparison to the control group. Interestingly, Vit C treatment reversed the mentioned effects of UCMS. Therefore, the latency to enter the dark chamber (P < 0. 05 and P < 0.01,1 and 24 h after the shock, PA test, UCMS + Vit C 400) and the time spent in the target quadrant (P < 0. 01 and P < 0.05, MWM test, UCMS + Vit C 400 and UCMS + Vit C 100, respectively) were longer in the UCMS + Vit C groups. Moreover, Vit C increased the content of thiol (P < 0.05, UCMS + Vit C 400), as well as the activity of catalase (P < 0.001, UCMS + Vit C 400) and superoxide dismutase (P < 0.0001, UCMS + Vit C 400, UCMS + Vit C 100), whereas the concentration of malondialdehyde (P < 0. 05 and P < 0.01, UCMS + Vit C 100, UCMS + Vit C 400) decreased in the hippocampal region of the brain in comparison to the UCMS group. Overall, these results suggest that Vit C could reverse UCMS-induced learning and memory impairment possibly through the modulation of brain OS.Key points Memory and learning impairments were induced by unpredictable chronic mild stress (UCMS)Vitamin C could prevent cognitive impairments caused by UCMS in rats by attenuation of oxidative stress in the brain.