Involvement of the serotonergic system and neuroplasticity in the antidepressant effect of curcumin in ovariectomized rats: Comparison with oestradiol and fluoxetine

Phytother Res. 2019 Feb;33(2):387-396. doi: 10.1002/ptr.6232. Epub 2018 Dec 21.


Antidepressant drugs are associated with many challenges due to their adverse impacts. Seeking alternatives through medicinal plants could have a great merit in overcoming these deleterious effects. This study was designed to investigate the potential mechanism of curcumin (CUR) in modifying the depression-like behaviour in ovariectomised (OVX) rats, inference with fluoxetine (FLX) and oestradiol (E2 ). The treatments of OVX rats started after 1 month post ovariectomy and proceeded for 1 month. The experimental animals were divided into five groups: sham-operated, OVX-, OVX-FLX (20 mg kg-1 , i.p., daily), OVX-E2 (100 μg kg-1 , i.m., every other day), and OVX-CUR- (100 mg kg-1 , p.o., daily) treated groups. The results showed that CUR modulated the depression-like behaviour using forced swimming test. It improved the serotonin content in many brain regions by upregulating tryptophan hydroxylase-2 and 5-hydroxytryptamine1A,2A receptor messenger RNA (mRNA) and downregulating monoamine oxidase A mRNA in the limbic system. Furthermore, it upregulated aromatase, brain-derived neurotropic factor mRNA, and extracellular-regulated kinase 1/2 protein in the limbic system, relative to FLX and E2, compared with OVX group. In conclusion, CUR appears to be safe and efficient agent as serotonin modulator similar to FLX and neurotrophic agent like E2 , in improving the depression-like behaviour in OVX rats.

Keywords: BDNF; ERK1/2; curcumin; fluoxetine; ovariectomy; serotonergic system.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Curcumin / pharmacology*
  • Depression / drug therapy*
  • Estradiol / pharmacology
  • Female
  • Fluoxetine / pharmacology
  • Neuronal Plasticity / drug effects*
  • Ovariectomy
  • Rats
  • Rats, Wistar
  • Swimming


  • Antidepressive Agents
  • Fluoxetine
  • Estradiol
  • Curcumin