Page 74 - ITPS-8-2

INNOSC Theranostics

and Pharmacological Sciences

ORIGINAL RESEARCH ARTICLE
Repeated ketamine doses elevate superoxide

dismutase activity in a pharmacological model
of schizophrenia-like phenotypes in mice

1
Yusuf Usman * , Adegbuyi Oladele Aderibigbe 2 , and Fatai Adewale Fehintola 2
1 Department of Pharmacology, Faculty of Basic Medical Sciences, Federal University of Health
Sciences Ila-Orangun, Ila-Orangun, Osun State, Nigeria
2 Department of Pharmacology, Faculty of Basic Medical Sciences University of Ibadan, Ibadan, Oyo
State, Nigeria

Abstract

This study evaluated behavioral phenotypes and superoxide dismutase (SOD)
enzymatic activity in a repeated sub-anesthetic dose of ketamine (KET) administered
to model schizophrenia in an animal study. The animals were divided into three
(3) experimental groups. The KET alone group received sub-anesthetic dose of
*Corresponding author:
Yusuf Usman KET (20 mg/kg) for 14 consecutive days. The control group vehicle (VEH) received
(usman.yusuf@fuhsi.edu.ng) distilled water (10 mL/kg) as a VEH, while the KET and risperidone (RISP) group (KET
+ RISP) received a sub-anesthetic dose of KET (20 mg/kg) alone for 7 consecutive
Citation: Usman Y, Aderibigbe AO,
Fehintola FA. Repeated days, followed by RISP (0.5 mg/kg) administered 1-h post-KET treatment from days
ketamine doses elevate 8 to 14. All treatments were administered intraperitoneally (i.p.). Twenty-four hours
superoxide dismutase activity after the last treatment, behavioral phenotypes (locomotor activity and cognition)
in a pharmacological model of
schizophrenia-like phenotypes were assessed using the locomotor activity cage and the elevated plus maze (EPM).
in mice. INNOSC Theranostics Thereafter, SOD enzymatic activity was evaluated in homogenized brain tissue
and Pharmacological Sciences. from each mouse using spectrophotometric analysis. Animals that received KET
2025;8(2):68-76.
doi: 10.36922/itps.6372 (20 mg/kg i.p) alone showed a significant (P < 0.05) increase in movement counts
and rearing events in the locomotor activity test. It also prolonged the latency to
Received: November 20, 2024
enter the open arms during the anxiety-induced cognitive assessment in the EPM,
1st revised: January 6, 2025 compared to animals that received distilled water or those that received KET and
2nd revised: January 14, 2025 RISP. SOD enzymatic activity was significantly elevated in the KET group compared to
the VEH and KET + RISP groups. The elevated SOD enzymatic activity may represent a
3rd revised: February 12, 2025
compensatory response to the oxidative stress induced by repeated sub-anesthetic
Accepted: February 17, 2025 doses of KET.
Published online: February 28,
2025
Keywords: Superoxide dismutase; Ketamine; Schizophrenia; Phenotypes; Mice; Model
Copyright: © 2025 Author(s).
This is an Open-Access article
distributed under the terms of the
Creative Commons Attribution
License, permitting distribution, 1. Introduction
and reproduction in any medium,
provided the original work is Superoxide dismutase (SOD) is an endogenous antioxidant enzyme that plays a critical
properly cited. role in converting superoxide radicals into less toxic hydrogen peroxide and oxygen
1
Publisher’s Note: AccScience molecules, thus protecting cells from oxidative damage. In schizophrenia, altered
Publishing remains neutral with SOD enzymatic activity has been observed, with studies showing both increased
regard to jurisdictional claims in
published maps and institutional and decreased activities, depending on the stage of the disease and treatment status,
2
affiliations with increased levels in first-episode schizophrenic patients. Changes in endogenous
Volume 8 Issue 2 (2025) 68 doi: 10.36922/itps.6372