Original Investigation

Psychopharmacology

, 201:435

First online:

Antidepressant activity of curcumin: involvement of serotonin and dopamine system

  • Shrinivas K. KulkarniAffiliated withPharmacology Division, University Institute of Pharmaceutical Sciences, Panjab UniversityCentre with Potential for Excellence in Biomedical Sciences (CPEBS), Panjab University Email author 
  • , Mohit Kumar BhutaniAffiliated withPharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University
  • , Mahendra BishnoiAffiliated withCentre with Potential for Excellence in Biomedical Sciences (CPEBS), Panjab University

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Abstract

Rationale

Curcumin is a major active principle of Curcuma longa, one of the widely used preparations in the Indian system of medicine. It is known for its diverse biological actions.

Objective

The present study was designed to investigate the involvement of monoaminergic system(s) in the antidepressant activity of curcumin and the effect of piperine, a bioavailability enhancer, on the bioavailability and biological effects of curcumin.

Methods and observations

Behavioral (forced swim test), biochemical (monoamine oxidase (MAO) enzyme inhibitory activity), and neurochemical (neurotransmitter levels estimation) tests were carried out. Curcumin (10–80 mg/kg, i.p.) dose dependently inhibited the immobility period, increased serotonin (5-hydroxytryptamine, 5-HT) as well as dopamine levels (at higher doses), and inhibited the monoamine oxidase enzymes (both MAO-A and MAO-B, higher doses) in mice. Curcumin (20 mg/kg, i.p.) enhanced the anti-immobility effect of subthreshold doses of various antidepressant drugs like fluoxetine, venlafaxine, or bupropion. However, no significant change in the anti-immobility effect of imipramine and desipramine was observed. Furthermore, combination of subthreshold dose of curcumin and various antidepressant drugs resulted in synergistic increase in serotonin (5-HT) levels as compared to their effect per se. There was no change in the norepinephrine levels. The coadministration of piperine (2.5 mg/kg, i.p.), a bioavailability enhancing agent, with curcumin (20 and 40 mg/kg, i.p.) resulted in potentiation of pharmacological, biochemical, and neurochemical activities.

Conclusion

The study provides evidences for mechanism-based antidepressant actions of curcumin. The coadministration of curcumin along with piperine may prove to be a useful and potent natural antidepressant approach in the management of depression.

Keywords

Curcumin Forced swim test (FST) Serotonin Monoamine oxidase (MAO) Piperine