Antidepressant-like activity of plumbagin in unstressed and stressed mice

Pharmacol Rep. 2015 Oct;67(5):1024-32. doi: 10.1016/j.pharep.2015.03.001. Epub 2015 Mar 19.

Abstract

Background: Plumbagin has been reported to be neuroprotective, so it might possess antidepressant activity. Therefore, the present study was designed to explore the antidepressant potential of plumbagin in unstressed and stressed mice.

Methods: Depression-like behavior was induced in Swiss male albino mice by subjecting them to unpredictable mild stress daily for 21 successive days. Plumbagin (4, 8 and 16mg/kg, po) and imipramine (15mg/kg, po) were administered for 3 successive weeks to separate groups of unstressed and stressed mice. Tail suspension test and sucrose preference test were used to evaluate antidepressant effect of the drugs.

Results: Highest dose (16mg/kg) of plumbagin and imipramine significantly decreased immobility period of unstressed and stressed mice in tail suspension test as compared to their respective controls. These drugs significantly restored the reduced sucrose preference (%) in stressed mice. The drugs did not significantly affect locomotor activity of mice. Antidepressant-like activity of plumbagin was found to be comparable to imipramine. Plumbagin and imipramine significantly inhibited brain MAO-A activity, decreased plasma nitrite, brain malondialdehyde and catalase levels; and increased reduced glutathione levels of unstressed and stressed mice. The drugs significantly reversed stress-induced increase in plasma corticosterone levels.

Conclusions: Antidepressant-like activity of plumbagin in unstressed and stressed mice might be through inhibition of brain MAO-A activity and improvement of antioxidant status. Reversal of stress-induced increase in plasma corticosterone levels might also be responsible for antidepressant-like activity of plumbagin in stressed mice.

Keywords: Antidepressant; Chronic unpredictable mild stress; Corticosterone; Depression; Plumbagin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Antidepressive Agents, Tricyclic / pharmacology
  • Antioxidants / metabolism
  • Behavior, Animal / drug effects
  • Brain / drug effects
  • Brain / enzymology
  • Corticosterone / metabolism
  • Depression / drug therapy*
  • Depression / etiology
  • Hindlimb Suspension / psychology
  • Imipramine / pharmacology
  • Male
  • Mice
  • Monoamine Oxidase / metabolism
  • Monoamine Oxidase Inhibitors / pharmacology
  • Motor Activity / drug effects
  • Naphthoquinones / pharmacology*
  • Stress, Psychological / complications
  • Stress, Psychological / psychology*

Substances

  • Antidepressive Agents
  • Antidepressive Agents, Tricyclic
  • Antioxidants
  • Monoamine Oxidase Inhibitors
  • Naphthoquinones
  • Monoamine Oxidase
  • Imipramine
  • Corticosterone
  • plumbagin