Antipsychotic activity of standardized Bacopa extract against ketamine-induced experimental psychosis in mice: Evidence for the involvement of dopaminergic, serotonergic, and cholinergic systems

Pharm Biol. 2015;53(12):1850-60. doi: 10.3109/13880209.2014.976350. Epub 2015 Apr 9.


Context: Schizophrenia is a chronic disabling psychiatric disorder affecting 1% of the population worldwide. Due to the adverse effects of available antipsychotic medications, recent investigations have focused on the search for well-tolerated, safe molecules from natural resources to control the severity and progression of schizophrenia.

Objective: To screen the standardized extract of Bacopa monniera Linn. (Scrophulariaceae) (BM) for its antipsychotic potential in the ketamine-induced psychosis model with mice.

Materials and methods: Graded dose of BM (40, 80, and 120 mg/kg, p.o.) were given to the mice 1 h prior to ketamine administration and tested for positive symptoms and cognitive deficits. A chronic ketamine treatment regimen was used to study the effect of BM on negative symptoms such as immobility enhancement. Each mouse was used once for the behavioral studies.

Results: BM reduced ketamine-induced hyperactivity with an EC50 value of 76.60 mg/kg. The 80 mg/kg dose was used for all other behavior analysis. Pretreatment with BM at 80 mg/kg showed two-fold increases in transfer latency time (TLT) in passive avoidance task. Chronic BM pretreatment (80 mg/kg p.o. daily × 10 d) ameliorated the ketamine-induced enhanced immobility effect by 21% in the forced swim test. BM treatment reversed ketamine-induced increase in monoamine oxidase activity in both cortex and striatum and normalized the acetylcholinesterase activity and the glutamate levels in the hippocampus.

Discussion and conclusion: Overall our findings suggest that BM possesses antipsychotic properties which might be due to its modulatory action on dopamine, serotonin, and glutamate neurotransmission.

Keywords: Bacopa monniera; forced swim test; locomotor activity; neurotransmitter; passive avoidance test.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipsychotic Agents / isolation & purification
  • Antipsychotic Agents / therapeutic use*
  • Bacopa*
  • Dopamine / metabolism*
  • Dose-Response Relationship, Drug
  • Glutamine / metabolism*
  • Ketamine / toxicity
  • Male
  • Mice
  • Plant Extracts / isolation & purification
  • Plant Extracts / therapeutic use
  • Psychotic Disorders / drug therapy
  • Psychotic Disorders / metabolism*
  • Serotonin / metabolism*


  • Antipsychotic Agents
  • Plant Extracts
  • Glutamine
  • Serotonin
  • Ketamine
  • Dopamine