Piperine protects epilepsy associated depression: a study on role of monoamines

Eur Rev Med Pharmacol Sci. 2011 Nov;15(11):1288-95.


Background and objectives: In patients with epilepsy, a common comorbidity diagnosed is depression. Temporal lobe epilepsy or post status epilepticus (SE) animal model establish and validate the co morbidity and common pathogenesis of depression and epilepsy. Elevation in serotonin concentration gives an inhibitory response to epileptic discharge and stabilizes the depressed mood disorder. Piperine is a potent monoaminooxidase inhibitor and stimulates the synthesis of serotonin. So the present work is undertaken to investigate the effect of piperine on depression associated with by status epilepticus induced by pilocarpine in rats.

Materials and methods: Status epilepticus was induced in the rats by administration of pilocarpine 350 mg/kg i.p.. Behaviour tests like forced swimming test (FST), saccharin consumption test, actophotometer test and rotarod test were conducted. Antidepressant effect and neuroprotective effect of piperine (25 mg/kg, p.o. for 10 days) in post status epilepticus animal model was evaluated. Brain serotonin concentration was also estimated. Fluoxetine (20 mg/kg p.o.) was used as standard.

Results: Only piperine but not fluoxetine significantly increased the decrease in number of rotations of wheel in FST, and decrease volume of saccharine consumption caused by pilocarpine. Both fluoxetine and piperine significantly increase the pilocarpine induced decrease in activity score in actophotometer, time taken to fall in rotarod and concentration of serotonin in brain.

Discussion: The underlying mechanism behind depression in epilepsy may be alteration in monoaminergic pathways and GABAergic pathways. The antidepressant activity of piperine in post-SE rats may be attributed to its MAO inhibitor activity and neuroprotective activity.

MeSH terms

  • Alkaloids / pharmacology*
  • Anhedonia / drug effects
  • Animals
  • Anticonvulsants / pharmacology*
  • Behavior, Animal / drug effects
  • Benzodioxoles / pharmacology*
  • Biogenic Monoamines / metabolism*
  • Brain Chemistry / drug effects
  • Chromatography, Thin Layer
  • Convulsants
  • Depression / etiology*
  • Depression / metabolism
  • Depression / prevention & control*
  • Epilepsy / chemically induced
  • Epilepsy / complications*
  • Epilepsy / drug therapy*
  • Female
  • Fluoxetine / pharmacology
  • Male
  • Motor Activity / drug effects
  • Pilocarpine
  • Piperidines / pharmacology*
  • Polyunsaturated Alkamides / pharmacology*
  • Postural Balance / drug effects
  • Rats
  • Serotonin / metabolism
  • Spectrophotometry, Infrared
  • Status Epilepticus / chemically induced
  • Status Epilepticus / psychology
  • Swimming / psychology


  • Alkaloids
  • Anticonvulsants
  • Benzodioxoles
  • Biogenic Monoamines
  • Convulsants
  • Piperidines
  • Polyunsaturated Alkamides
  • Fluoxetine
  • Pilocarpine
  • Serotonin
  • piperine