title: Neuroprotective effects of the ethanol stem bark extracts of Terminalia ivorensis in ketamine-induced schizophrenia-like behaviors and oxidative damage in mice.
abstract: BACKGROUND
  Schizophrenia is a heterogenous neurological disorder, which has been hypothetically linked to oxidative imbalance and associated behavioral perturbations. Preliminary evidence from animal models predictive of human psychosis suggests that Terminalia ivorensis A. Chev. (Combretaceae) has antipsychotic-like activity in mice.
  
  
  OBJECTIVE
  This study investigates the neuroprotective property of the ethanol stem bark extracts of T. ivorensis (EETI) in reversal treatment of ketamine-induced schizophrenia-like behaviors and oxidative alteration in adult male Swiss albino mice.
  
  
  METHODS
  Animals were divided into six treatment groups (n = 5). Animals received distilled water or ketamine (20 mg/kg) once daily intraperitoneally (i.p.) for 14 days, and from the 8th to the 14th day, they were treated with EETI (125, 250 or 500 mg/kg), risperidone (RIS) or vehicle orally once daily. Behaviors related to positive (locomotor activity) and cognitive (Y maze) symptoms of schizophrenia were assessed. Glutathione (GSH) levels, superoxide dismutase (SOD) and catalase (CAT) activities, including malondialdehyde (MDA) concentration were measured in mice whole brains.
  
  
  RESULTS
  The LD50of EETI was 2236.06 mg/kg, p.o. body weight. EETI (125, 250 or 500 mg/kg, p.o.) demonstrated significant (p < 0.05) inhibition of ketamine-induced hyperlocomotion and cognitive dysfunction. The extract decreased MDA concentration (39.0, 62.6 and 67.5%) in a dose-dependent manner. Moreover, EETI significantly (p < 0.05) reversed the depletion of GSH, and increased activities of SOD and CAT in brain tissues.
  
  
  CONCLUSIONS
  These findings suggest that EETI probably exert its antipsychotic-like activity, via a neuroprotective compensatory mechanism of action, and as such, could be relevant in the management of schizophrenia.
authors.affiliation: a Department of Pharmacology and Therapeutics, College of Medicine , University of Ibadan , Ibadan , Oyo State , Nigeria.
authors.forename: Benneth
authors.initials: B
authors.lastname: Ben-Azu
authors.affiliation: a Department of Pharmacology and Therapeutics, College of Medicine , University of Ibadan , Ibadan , Oyo State , Nigeria.
authors.forename: Adegbuyi Oladele
authors.initials: AO
authors.lastname: Aderibigbe
authors.affiliation: a Department of Pharmacology and Therapeutics, College of Medicine , University of Ibadan , Ibadan , Oyo State , Nigeria.
authors.forename: Abayomi Mayowa
authors.initials: AM
authors.lastname: Ajayi
authors.affiliation: a Department of Pharmacology and Therapeutics, College of Medicine , University of Ibadan , Ibadan , Oyo State , Nigeria.
authors.forename: Ezekiel Oluwagbenga
authors.initials: EO
authors.lastname: Iwalewa
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology / Q000627:therapeutic use; D007649:Ketamine / Q000633:toxicity*; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D024301:Plant Bark; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D018547:Plant Stems; D012559:Schizophrenia / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D029766:Terminalia; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D018696:Neuroprotective Agents; D010936:Plant Extracts; D000431:Ethanol; D007649:Ketamine
keywords: Antipsychotics; antioxidants; neuroprotection; psychosis