Ascorbic acid protects against restraint stress-induced memory deficits in Wistar rats

Abstract

Objective: Chronic stress has been shown to cause oxidative damage in the central nervous system. Although stress-induced impairments in learning and memory have been studied extensively, very few studies have investigated possible ways to prevent their ill effects. The present work was designed to study the protective effects of ascorbic acid in memory loss induced by chronic restraint stress.

Methods: Adult male Wistar rats were designated into the following groups: (i) Normal control, (ii) Ascorbic acid treatment, (iii) Vehicle control, (iv) Restraint stress, (v) Restraint stress + vehicle, and (vi) Restraint stress + ascorbic acid treatment. At the end of 21 days, animals of all groups were subjected to memory tests using Morris water maze and passive avoidance apparatus. Then, the results obtained were compared between the experimental groups.

Results: Rats exposed to restraint stress alone and those pretreated with vehicle solution before restrained stress showed deficits in learning and impaired memory retention in the memory tests when compared to animals in other experimental groups. Animals pretreated with ascorbic acid before restraining showed significant improvement in memory retention in the same memory tests.

Conclusions: Results of this study suggest the possibility of using ascorbic acid as a dietary supplement to prevent stress-induced memory impairments.

Keywords: Ascorbic acid; Passive avoidance; Restraint stress; Spatial memory; Water maze.

Figure 1

Latency to enter the dark compartment of passive avoidance apparatus during memory retention test after 24 and 48 hr. Data represent mean ± SEM (n=6). Normal control/vehicle control vs. stressed, $ P<0.001; stressed vs. stressed + ascorbic acid treated, # P<0.001; stressed + vehicle vs. stressed + ascorbic acid treated, ≤ P<0.001; control vs. ascorbic acid treated, ∂ P<0.01; vehicle control vs. ascorbic acid,* P<0.05; after 24 hrs and 48 hrs, one-way ANOVA, Tukey (post-hoc)

Figure 2

A - Progressive learning of rats in different groups during six successive days of water maze training (Fig. 2A). Data represent mean ± SEM (n=6). Normal control/vehicle control vs. stressed, $ P<0.001; stressed vs. stressed + ascorbic acid treated # P<0.001, stressed+ vehicle vs. stressed+ ascorbic acid treated, £ P<0.001; from day 2 to day 6; normal control/vehicle control vs. ascorbic acid treated, on day three,* P<0.05; analysis of variance (ANOVA) with repeated measures followed by Bonferroni (post-hoc). B - Latency to enter the target quadrant during the probe trial. Data represent mean ± SEM (n=6). Normal control vs. stressed, $ P <0.001; stressed vs. stressed + ascorbic acid treated, # P <0.001; stressed+ vehicle vs. stressed+ ascorbic acid treated, £ P<0.001; normal control vs. ascorbic acid treated, ∂ P<0.01; vehicle control vs. ascorbic acid treated,* P<0.01; one-way ANOVA, Tukey (post-hoc). C - Time spent in the target quadrant during the probe trial. Data represent mean ± SEM (n=6). Normal control/vehicle control vs. stressed, $ P<0.001; stressed vs. stressed + ascorbic acid treated # P<0.001, stressed + vehicle control vs. stressed + ascorbic acid treated, £ P<0.001; normal control vs. ascorbic acid treated, ∂ P<0.05; vehicle control vs. ascorbic acid treated,* P<0.01; one-way ANOVA, Tukey (post-hoc). D - Distance traveled in the target quadrant during probe trial test. All data represent mean ± SEM (n=6); normal control vs. stressed, P<0.001; stressed vs. stressed +ascorbic acid treated, P<0.001; stressed+ vehicle vs. stressed+ ascorbic acid treated, £ P<0.001; one-way ANOVA, Tukey test (post-hoc)

Figure 3

Video tracking of swim paths taken by a representative rat in each group with respect to time spent in the former location of the platform during the probe trial. Normal control (NC), vehicle control (V), ascorbic acid (AA), stressed (S), stressed+ vehicle (S+V) stressed + ascorbic acid treated (S+AA) rats. Note that stressed rats spent less time in the target quadrant (TQ), unlike stressed + ascorbic acid-treated rats, which spent most of their time there. B- beginning, E- end of the tracking