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

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 (E-2). 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-E-2 (100 mu g 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-hydroxytryptamine(1A,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 E-2,E- compared with OVX group. In conclusion, CUR appears to be safe and efficient agent as serotonin modulator similar to FLX and neurotrophic agent like E-2, in improving the depression-like behaviour in OVX rats.