Involvement of serotonergic system in the antidepressant-like effect of piperine

Prog Neuropsychopharmacol Biol Psychiatry. 2011 Jun 1;35(4):1144-7. doi: 10.1016/j.pnpbp.2011.03.017. Epub 2011 Apr 6.


Piperine is a major alkaloid of black pepper (Piper nigrum Linn.) and long pepper (P. longum Linn.), and its antidepressant-like effect has been previously demonstrated. The purpose of this study was to explore the possible contribution of the serotonergic system in the antidepressant-like effect of piperine in mice. The results showed that piperine significantly reduced the immobility time in the forced swim test and tail suspension test in mice. The anti-immobility effect of piperine in the forced swim test and tail suspension test was completely abolished by pre-treating the mice with pCPA (an inhibitor of 5-HT synthesis). Piperine treatment also significantly potentiated the number of head-twitches of mice induced by 5-HTP (a metabolic precursor to 5-HT). In addition, the neurochemical assays showed that piperine produced a marked increase of 5-HT level in both the hippocampus and frontal cortex of mice. Taken together, these results clearly suggest that the antidepressant-like effect of piperine is mediated via the serotonergic system by enhancing 5-HT content in mouse brain.

MeSH terms

  • 5-Hydroxytryptophan / pharmacology
  • Alkaloids / pharmacology*
  • Analysis of Variance
  • Animals
  • Antidepressive Agents*
  • Behavior, Animal / drug effects
  • Benzodioxoles / pharmacology*
  • Brain Chemistry / drug effects
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Fenclonine / pharmacology
  • Fluoxetine / pharmacology
  • Hindlimb Suspension / psychology
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Male
  • Mice
  • Mice, Inbred ICR
  • Piperidines / pharmacology*
  • Polyunsaturated Alkamides / pharmacology*
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Serotonin / metabolism
  • Serotonin / physiology*
  • Swimming / psychology


  • Alkaloids
  • Antidepressive Agents
  • Benzodioxoles
  • Piperidines
  • Polyunsaturated Alkamides
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Serotonin
  • 5-Hydroxytryptophan
  • Fenclonine
  • piperine