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INNOSC Theranostics and
Pharmacological Sciences Ketamine and SOD activity in schizophrenia

in the pathogenesis of schizophrenia, limited research 2.3. Dose selection
has explored its association with psychopathological Doses administered were based on previous studies
symptoms. Notably, studies have revealed a significant that demonstrated the induction of schizophrenia-
positive correlation between SOD enzymatic activity and like behaviors and altered oxidative stress in murine
symptom severity across the positive, negative, and general models. KET (20 mg/kg) was administered to the KET
6,26
psychopathology subscales of the positive and negative group and RISP (0.5 mg/kg) was given along with KET
syndrome scale in chronic schizophrenia patients. to the KET + RISP group, and distilled water (10 mL/kg)
23
Elevated SOD enzymatic activity has also been linked to was administered to the Vehicle (VEH) group as the
impaired cognitive performance, particularly in memory VEH, based on previously established protocols. KET
6
and decision-making tasks, as observed in the Y-Maze and was diluted in distilled water (VEH) and administered
locomotor behavior in an OFT. 24 intraperitoneally (i.p.) as previously described. Similarly,
26
Neuroprotective effects of atypical antipsychotics in RISP was dissolved in the VEH before intraperitoneal
addressing the underlying pathophysiological mechanisms (i.p.) administration. 6,26
of the disorder have been reported. These therapeutic
effects could be attributed to their role in microglial 2.4. Experimental design
activation or maintenance of antioxidant mechanisms Male and female mice were randomly assigned to one
in the cerebral cortex and hippocampus. 25,26 This study of three groups: control (VEH), KET, or KET and RISP
examines the effects of repeated sub-anesthetic doses (KET + RISP), with no sex-specific ratio, as previously
6
of KET administration on SOD enzymatic activity and used. The KET group received sub-anesthetic dose of
schizophrenia-like behaviors in mice. Hyperactivity was KET (20 mg/kg, i.p.) alone once daily for 14 consecutive
measured in the OFT, while spatial working memory, as an days. The control group (VEH) was given distilled water
indicator of cognitive dysfunction, was assessed with the (10 mL/kg, i.p.) for the duration of the experiment.
EPM. These assessments provide insights into hyperactivity Animals in the KET and RISP (KET + RISP) group were
and anxiety-induced poor exploratory performance as pre-treated with KET (20 mg/kg, i.p.) from day 1 to day 7
representations of positive and cognitive symptoms of and received RISP (0.5 mg/kg, i.p.) from the day 8 to day
schizophrenia in an animal model, respectively. 14, 1 h after KET administration. 22
2. Materials and methods 2.4.1. Behavioral assessments

2.1. Animals Twenty-four hours after the last treatment, each mouse was
subjected to behavioral tests to assess schizophrenia-like
Male and female Swiss mice at postnatal days 56 – symptoms. Hyperactivity was evaluated using the OFT,
70 (8 – 10 weeks) used for this study were obtained from the while cognitive deficits were evaluated using the EPM, as
Department of Pharmacology and Therapeutics Animal previously described with some modifications. 25-27 Each
House, Faculty of Basic Medical Sciences, University of animal was tested individually, beginning with the OFT,
Ibadan (Ibadan, Nigeria). They were housed in plastic cages followed by the EPM.
under standard laboratory conditions (12 h light/dark
cycle, temperature range of 25 ± 2°C, and relative humidity 2.4.2. OFT
of 60 ± 5). The mice were provided with a standard diet and Hyperactivity was evaluated in an open field apparatus for
water ad libitum. They were acclimatized in the laboratory 5 min, as previously described, with minor modifications.
26
for 2 weeks before the experimental procedure. The animals Briefly, spontaneous locomotor activity was measured in
were handled according to the institutional-based research an activity cage (Ugo Basile, Varese, Italy) with dimensions
ethics committee and National Institutes of Health (NIH) of 39 × 28 × 26 cm, featuring a front-view glass wall. The
guidelines for the use and care of laboratory animals. movement activity of each mouse was automatically recorded
by the activity cage for 5 min. Data were presented as the
2.2. Drugs and chemicals
number of horizontal and vertical motor activities measured
KET hydrochloride (Ranbaxy Pharm. Nigeria), RISP by the apparatus in response to animal movements, and the
(Afrab Chem, Nigeria), carbonate buffer, pH 9.5, 200 mM number of times each mouse raises the forelimbs (rearing),
(G-Biosciences, St Louis, USA), phosphate buffer solution, respectively. The apparatus was thoroughly cleaned with
1.0 M, pH 7.4 (Sigma-Aldrich, USA), and adrenaline 70% ethanol before introducing subsequent mouse. Before
(Sigma-Aldrich, USA) were used in this study. All the locomotor activity test, each animal was habituated to
chemicals and drugs were of analytical and pharmaceutical the activity cage (Ugo Basile, Varese, Italy) for 10 min daily
grades, respectively. over 3 consecutive days after chronic KET administration.

Volume 8 Issue 2 (2025) 70 doi: 10.36922/itps.6372