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

Psychopharmacology (Berl). 2002 Nov;164(2):233-5. doi: 10.1007/s00213-002-1253-5. Epub 2002 Sep 13.


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.

Publication types

  • Comparative Study

MeSH terms

  • Analysis of Variance
  • Animals
  • Animals, Outbred Strains
  • Antioxidants / pharmacology*
  • Behavior, Animal / drug effects*
  • Caffeic Acids / pharmacology*
  • Cinnamates / pharmacology*
  • Conditioning, Psychological / drug effects*
  • Depsides
  • Dose-Response Relationship, Drug
  • Fear / drug effects*
  • Male
  • Mice
  • Motor Activity / drug effects
  • Plant Extracts / chemistry


  • Antioxidants
  • Caffeic Acids
  • Cinnamates
  • Depsides
  • Plant Extracts
  • rosmarinic acid
  • caffeic acid