Repeated ketamine doses elevate superoxide dismutase activity in a pharmacological model of schizophrenia-like phenotypes in mice
Yusuf Usman, Adegbuyi Oladele Aderibigbe, Fatai Adewale Fehintola
INNOSC Theranostics and Pharmacological Sciences February 28, 2025 DOI: 10.36922/itps.6372 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | Ketamine Risperidone |
| Dose | 20 mg/kg ketamine; 0.5 mg/kg risperidone |
| Duration | 14-day treatment period; behavioral and biochemical assessments 24 hours after last treatment |
| Topics | Esketamine Ketamine |
| Key points | Repeated sub-anesthetic ketamine increased locomotor activity, anxiety-like behavior, and brain SOD activity in mice, all of which were attenuated by subsequent risperidone treatment. |
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 KET (20 mg/kg) for 14 consecutive days. The control group vehicle (VEH) received 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 days, followed by RISP (0.5 mg/kg) administered 1-h post-KET treatment from days 8 to 14. All treatments were administered intraperitoneally (i.p.). Twenty-four hours after the last treatment, behavioral phenotypes (locomotor activity and cognition) were assessed using the locomotor activity cage and the elevated plus maze (EPM). Thereafter, SOD enzymatic activity was evaluated in homogenized brain tissue from each mouse using spectrophotometric analysis. Animals that received KET (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 enter the open arms during the anxiety-induced cognitive assessment in the EPM, compared to animals that received distilled water or those that received KET and 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 compensatory response to the oxidative stress induced by repeated sub-anesthetic doses of KET.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |