Rosmarinus officinalis L. hydroalcoholic extract, similar to fluoxetine, reverses depressive-like behavior without altering learning deficit in olfactory bulbectomized mice

J Ethnopharmacol. 2012 Aug 30;143(1):158-69. doi: 10.1016/j.jep.2012.06.017. Epub 2012 Jun 18.


Ethnopharmacological relevance: Rosemary, Rosmarinus officinalis L., has several therapeutic applications in folk medicine for the treatment of a wide range of diseases, including depression.

Aim of the study: To evaluate the ability of Rosmarinus officinalis hydroalcoholic extract (ROHE), as compared to the positive control fluoxetine, to reverse behavioral (hyperactivity, anhedonic behavior and learning deficit in water maze) and biochemical alterations (serum glucose level and acetylcholinesterase, AChE, activity) induced by an animal model of depression, the olfactory bulbectomy (OB) in mice.

Materials and methods: Locomotor and exploratory behavior was assessed in the open-field, novel object and novel cage tests, anhedonic behavior was assessed in the splash test; cognitive deficits were evaluated in the water maze task. For the first set of experiments, ROHE (10-300 mg/kg) or fluoxetine (10mg/kg) was administered once daily (p.o.) for 14 days after OB and the behavioral tests were performed. For the second set of experiments, serum glucose and hippocampal and cerebrocortical AChE activity were determined in OB and SHAM-operated mice treated orally with ROHE (10mg/kg), fluoxetine (10mg/kg) or vehicle.

Results: ROHE (10-300 mg/kg), similar to fluoxetine, reversed OB-induced hyperactivity, increased exploratory and anhedonic behavior. OB needed significantly more trials in the training session to acquire the spatial information, but they displayed a similar profile to that of SHAM mice in the test session (24h later), demonstrating a selective deficit in spatial learning, which was not reversed by ROHE or fluoxetine. A reduced serum glucose level and an increased hippocampal AChE activity were observed in bulbectomized mice; only the latter effect was reversed by fluoxetine, while both effects were reversed by ROHE.

Conclusions: ROHE exerted an antidepressant-like effect in bulbectomized mice and was able to abolish AchE alterations and hypoglycemia, but not spatial learning deficit induced by OB. Overall, results suggest the potential of Rosmarinus officinalis for the treatment of depression, validating the traditional use of this plant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Behavior, Animal / drug effects*
  • Blood Glucose / metabolism
  • Depression / complications
  • Depression / drug therapy*
  • Depression / metabolism
  • Exploratory Behavior / drug effects
  • Female
  • Fluoxetine / pharmacology
  • Fluoxetine / therapeutic use
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hyperkinesis / drug therapy
  • Hyperkinesis / etiology
  • Hyperkinesis / metabolism
  • Hypoglycemia / drug therapy
  • Learning / drug effects*
  • Learning Disabilities / drug therapy
  • Learning Disabilities / etiology
  • Learning Disabilities / metabolism*
  • Mice
  • Mice, Inbred Strains
  • Olfactory Bulb / surgery
  • Phytotherapy*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Rosmarinus*


  • Antidepressive Agents
  • Blood Glucose
  • Plant Extracts
  • Fluoxetine
  • Acetylcholinesterase