Ascorbic acid presents rapid behavioral and hippocampal synaptic plasticity effects

Growing evidence has suggested that ascorbic acid may exhibit rapid anxiolytic and antidepressant-like effects. In this study the effects of a single administration of ascorbic acid (1 mg/kg, p.o.), ketamine (1 mg/kg, i.p., a fast-acting antidepressant) and fluoxetine (10 mg/kg, p.o., conventional antidepressant) were investigated on: a) behavioral performance in the novelty suppressed feeding (NSF) test; b) hippocampal synaptic protein immunocontent; c) dendritic spine density and morphology in the dorsal and ventral dentate gyrus (DG) of the hippocampus and d) hippocampal dendritic arborization. Ascorbic acid or ketamine, but not fluoxetine, decreased the latency to feed in the NSF test in mice. This effect was accompanied by increased p70S6K (Thr389) phosphorylation 1 h after ascorbic acid or ketamine treatment, although only ascorbic acid increased synapsin I immunocontent. Ketamine administration increased the dendritic spine density in the dorsal DG, but none of the treatments affected the maturation of dendritic spines in this region. In addition, both ascorbic acid and ketamine increased the dendritic spine density in the ventral DG, particularly the mature spines. Sholl analysis demonstrated no effect of any treatment on hippocampal dendritic arborization. Altogether, the results provide evidence that the behavioral and synaptic responses observed following ascorbic acid administration might occur via the upregulation of synaptic proteins, dendritic spine density, and maturation in the ventral DG, similar to ketamine. These findings contribute to understand the cellular targets implicated in its antidepressant/anxiolytic behavioral responses and support the notion that ascorbic acid may share with ketamine the ability to increase synaptic function.