Rosmarinic acid and caffeic acid reduce the defensive freezing behavior of mice exposed to conditioned fear stress

Rationale: We previously showed that rosmarinic acid from the leaves of Perilla frutescens Britton var. acuta Kudo (Perillae Herba) and its major metabolite caffeic acid have antidepressive-like activity in the forced swimming test. Objective: The present study was designed to examine whether rosmarinic acid and caffeic acid might also be effective in other types of stress model. Methods: The conditioned fear stress paradigm was used as a stress model for assessing the effects of rosmarinic acid and caffeic acid. Results: Rosmarinic acid (0.25-4 mg/kg, IP) induced a dose-dependent, U-shaped reduction in the duration of the defensive freezing behavior of mice exposed to conditioned fear stress. Caffeic acid (1-8 mg/kg, IP) also dose-dependently reduced this freezing behavior. However, neither substance, at doses that produced a significant reduction in the freezing behavior, affected spontaneous motor activity. Conclusions: These results confirm that rosmarinic acid and caffeic acid may inhibit the emotional abnormality produced by stress.