Anxiolysis and recognition memory enhancement with long-term supplemental ascorbic acid (vitamin C) in normal rats: possible dose dependency and sex differences

To investigate a possible dose-response relationship and sex differences for anxiolytic and memory-enhancing effects of ascorbic acid (vitamin C), an adult PVG /c hooded rats were individually treated for 8 weeks with approximately 61, 114 or 160 mg/kg/ day of ascorbic acid in their drinking water. After their treatment, over 3 consecutive days they experienced a 5-min trial in an open field (OF) followed by a 5-min trial in an elevated plus maze (EPM), and then finally a 5-min novel object recognition (NOR) test in the OF. Dose-related anxiolytic effects were observed that to some extent depended on the measure of anxiety. In other words, anxiolytic effects were evident in higher frequencies of walking with 114 mg/kg and 61 mg/kg, higher frequencies of rearing and lower frequencies of grooming in the OF as well as more frequent occupation of the EPM open arms. Rats treated with 160 mg/kg explored a novel versus familiar object in the NOR test to a significantly greater extent than control rats thereby suggesting enhancement of their recognition memory. Overall, it appeared that the anxiolytic effects of ascorbic acid were more typical of the lowest dose, whereas memory enhancement appeared to be confined to the highest dose. While there were a number of significant sex differences, there was no evidence of differences between females and males in the effects of ascorbic acid.