Anxiolytic effects of ascorbic acid and ketamine in mice

Some studies have demonstrated that ascorbic acid, similarly to ketamine, exhibits antidepressant-like effects mediated, at least in part, by modulation of the glutamatergic system. Despite the involvement of glutamatergic system in the pathophysiology of anxiety disorders, the ability of ascorbic acid and ketamine to elicit anxiolytic effects in animal models remains to be established. Therefore, this study investigated the effects of a single administration of ascorbic acid, ketamine or diazepam (positive control) in different animal models of anxiety. Mice were treated with ascorbic acid (1, 3 and 10 mg/kg, p.o.), ketamine (1 and 10 mg/kg, i.p.) or diazepam (2 mg/kg, p.o) and their behavioral responses were assessed in the elevated plus maze, open field test (OFT), ligh/dark preference test and marble burying test. Ascorbic acid increased total time spent in the open arms of elevated plus maze, increased total time in the center of the OFT, decreased rearing responses, increased the latency to grooming, decreased the rostral grooming, but did not affect body grooming. Furthermore, ascorbic acid increased the latency time and total time in light area in the ligh/dark preference test, but did not affect the performance of mice in the marble burying test. Ketamine demonstrated an anxiolytic-like effect in elevated plus maze, OFT, and ligh/dark preference test. Diazepam exhibited an anxiolytic-like effect in all the behavioral tests. Altogether, the results indicate the potential anxiolytic effect of ascorbic acid and ketamine, providing a possible new avenue for the management of anxiety-related disorders.