Protective effects of stigmasterol against ketamine-induced psychotic symptoms: Possible behavioral, biochemical and histopathological changes in mice

Pharmacol Rep. 2018 Jun;70(3):591-599. doi: 10.1016/j.pharep.2018.01.001. Epub 2018 Jan 11.

Abstract

Background: Stigmasterol, a naturally occurring phytoestrogen has been reported to possess many pharmacological activities. The aim of the present study was to screen the effect of stigmasterol against ketamine-induced mice model of psychosis.

Methods: The behavioural studies included an assessment of locomotor activity, stereotypic behaviours, immobility duration, step down latency and effects on catalepsy. Biochemical estimations involved the estimations of GABA, dopamine, GSH, MDA, TNF-α, total protein content and AChE activity. Histopathological changes and effect on androgenic parameters were also evaluated.

Results: Stigmasterol treated animals showed significant decrease in locomotor activity, stereotypic behaviours, immobility duration and increased step down latency. Biochemical estimations revealed increased GABA, GSH levels and decreased dopamine, MDA, TNF-α levels and AChE activity. These findings were confirmed by histopathological changes in the cortex part of the brain. Further, stigmasterol was not found to cause catalepsy and any adverse effect on the reproductive system.

Conclusion: This study concluded that stigmasterol could ameliorate ketamine-induced behavioral, biochemical and histopathological alterations in mice showing its potential effects in the management of psychotic symptoms.

Keywords: Ketamine; Oxidative stress; Phytosterol; Psychosis; Stigmasterol.

MeSH terms

  • Acetylcholine / metabolism
  • Animals
  • Antipsychotic Agents / pharmacology*
  • Brain / drug effects
  • Brain / metabolism
  • Catalepsy / drug therapy
  • Catalepsy / metabolism
  • Disease Models, Animal
  • Dopamine / metabolism
  • Glutathione / metabolism
  • Ketamine / pharmacology
  • Male
  • Malondialdehyde / metabolism
  • Mice
  • Motor Activity / drug effects
  • Oxidative Stress / drug effects
  • Protective Agents / pharmacology*
  • Psychotic Disorders / drug therapy*
  • Psychotic Disorders / metabolism
  • Stigmasterol / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Antipsychotic Agents
  • Protective Agents
  • Tumor Necrosis Factor-alpha
  • Malondialdehyde
  • gamma-Aminobutyric Acid
  • Ketamine
  • Stigmasterol
  • Glutathione
  • Acetylcholine
  • Dopamine