Antidepressant Activity of Curcumin: Involvement of Serotonin and Dopamine System

Psychopharmacology (Berl). 2008 Dec;201(3):435-42. doi: 10.1007/s00213-008-1300-y. Epub 2008 Sep 3.

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.

MeSH terms

  • Alkaloids / pharmacology
  • Animals
  • Antidepressive Agents / chemistry
  • Antidepressive Agents / pharmacology*
  • Behavior, Animal / drug effects
  • Benzodioxoles / pharmacology
  • Biogenic Monoamines / physiology
  • Biological Availability
  • Curcumin / chemistry
  • Curcumin / pharmacology*
  • Dopamine / physiology*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Drug Therapy, Combination
  • Immobility Response, Tonic / drug effects
  • Immobility Response, Tonic / physiology
  • Injections, Intraperitoneal
  • Male
  • Mice
  • Mice, Inbred Strains
  • Monoamine Oxidase / drug effects
  • Monoamine Oxidase Inhibitors / pharmacology
  • Piperidines / pharmacology
  • Polyunsaturated Alkamides / pharmacology
  • Reserpine / adverse effects
  • Reserpine / antagonists & inhibitors
  • Selegiline / pharmacology
  • Serotonin / physiology*
  • Swimming / psychology
  • Time Factors
  • Tranylcypromine / pharmacology

Substances

  • Alkaloids
  • Antidepressive Agents
  • Benzodioxoles
  • Biogenic Monoamines
  • Monoamine Oxidase Inhibitors
  • Piperidines
  • Polyunsaturated Alkamides
  • Selegiline
  • Serotonin
  • Tranylcypromine
  • Reserpine
  • Monoamine Oxidase
  • Curcumin
  • piperine
  • Dopamine