Although some central effects of citral have been reported, cognitive effects on spatial memory have not been investigated. The evidence showed that citral can regulate the synthesis of retinoic acid (RA), which exerts a vital function in the development and maintenance of spatial memory. In this study, we applied Morris water maze to test the effect of citral on animals' spatial learning and memory. To elucidate the mechanism of this effect, we also measured the retinoic acid concentration in rats' hippocampus by high performance liquid chromatography (HPLC). Our data implied biphasic effects of citral. The low dose (0.1 mg/kg) of citral improved the spatial learning capability, and enhanced the spatial reference memory of rats, whereas the high dose (1.0 mg/kg) was like to produce the opposite effects. Meanwhile, the low dose of citral increased the hippocampal retinoic acid concentration, while the high dose decreased it. Due to the quick elimination and non-bioaccumulation in the body, effects of citral on spatial memory in this study seemed to be indirect actions. The change in hippocampal retinoic acid concentration induced by different doses of citral might be responsible for the biphasic effect of citral on spatial learning and memory.
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