On the mechanism of antidepressant-like action of berberine chloride

Eur J Pharmacol. 2008 Jul 28;589(1-3):163-72. doi: 10.1016/j.ejphar.2008.05.043. Epub 2008 Jun 3.


Berberine, an alkaloid isolated from Berberis aristata Linn. has been used in the Indian system of medicines as a stomachic, bitter tonic, antiamoebic and also in the treatment of oriental sores. Evidences have demonstrated that berberine possesses central nervous system activities, particularly the ability to inhibit monoamine oxidase-A, an enzyme involved in the degradation of norepinephrine and serotonin (5-HT). With this background, the present study was carried out to elucidate the antidepressant-like effect of berberine chloride in different behavioural paradigms of despair. Berberine (5, 10, 20 mg/kg, i.p.) inhibited the immobility period in mice in both forced swim and tail-suspension test, however, the effect was not dose-dependent. Berberine (5 and 10 mg/kg, i.p.) also reversed the reserpine-induced behavioral despair. Berberine (5 mg/kg, i.p.) enhanced the anti-immobility effect of subeffective doses of various typical but not atypical antidepressant drugs in forced swim test. Berberine (5 mg/kg, i.p.) following its acute administration in mice resulted in increased levels of norepinephrine (31%), serotonin (47%) and dopamine (31%) in the whole brain. Chronic administration of berberine (5 mg/kg, i.p.) for 15 days significantly increased the levels of norepinephrine (29%), serotonin (19%) as well as dopamine (52%) but at higher dose (10 mg/kg, i.p.), there was no change in the norepinephrine (12%) levels but a significant increase in the serotonin (53%) and dopamine (31%) levels was found. The antidepressant-like effect of berberine (5 mg/kg, i.p.) in forced swim test was prevented by pretreatment with l-arginine (750 mg/kg, i.p.) or sildenafil (5 mg/kg, i.p.). On the contrary, pretreatment of mice with 7-nitroindazole (7-NI) (25 mg/kg, i.p.) or methylene blue (10 mg/kg, i.p.) potentiated the effect of berberine (2 mg/kg, i.p.) in the forced swim test. Pretreatment of mice with (+)-pentazocine (2.5 mg/kg, i.p.), a high-affinity sigma1 receptor agonist, produced synergism with subeffective dose of berberine (2 mg/kg, i.p.). Pretreatment with various sigma receptor antagonists viz. progesterone (10 mg/kg, s.c.), rimcazole (5 mg/kg, i.p.) and N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine (BD1047; 1 mg/kg, i.p.) reversed the anti-immobility effects of berberine (5 mg/kg, i.p.). Berberine at lower dose did not affect the locomotor activity and barbiturate-induced sleep time. It produced mild hypothermic action in rats and displayed analgesic effect in mice. Taken together, theses findings demonstrate that berberine exerted antidepressant-like effect in various behavioural paradigms of despair possibly by modulating brain biogenic amines (norepinephrine, serotonin and dopamine). Further, nitric oxide pathway and/or sigma receptors are involved in mediating its antidepressant-like activity in mouse forced swim test.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / pharmacology
  • Animals
  • Antidepressive Agents / pharmacology*
  • Behavior, Animal / drug effects*
  • Berberine / analogs & derivatives
  • Berberine / pharmacology*
  • Body Temperature / drug effects
  • Brain / drug effects*
  • Brain / metabolism
  • Depression / chemically induced
  • Depression / drug therapy*
  • Depression / psychology
  • Disease Models, Animal
  • Dopamine / metabolism
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Drug Therapy, Combination
  • Hot Temperature
  • Male
  • Mice
  • Motor Activity / drug effects
  • Nitric Oxide / metabolism
  • Norepinephrine / metabolism
  • Pain / etiology
  • Pain / physiopathology
  • Pain / prevention & control
  • Pain Measurement
  • Pain Threshold / drug effects
  • Rats
  • Rats, Wistar
  • Receptors, sigma / drug effects
  • Receptors, sigma / metabolism
  • Reserpine
  • Serotonin / metabolism
  • Sigma-1 Receptor
  • Sleep / drug effects
  • Swimming
  • Time Factors
  • Up-Regulation


  • Analgesics
  • Antidepressive Agents
  • Receptors, sigma
  • Berberine
  • Nitric Oxide
  • Serotonin
  • Reserpine
  • Dopamine
  • Norepinephrine