Influence of the dose of ketamine used on schizophrenia-like symptoms in mice: A correlation study with TH, GAD67, and PPAR-γ.
Talita Rodrigues, Getulio Nicola Bressan, Barbara Krum, F. A. Soares, Roselei Fachinetto
Pharmacology, Biochemistry, and Behavior October 1, 2023 DOI: 10.1016/j.pbb.2023.173658 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Male mice |
| Intervention | Ketamine |
| Dose | 20-40 mg/kg |
| Duration | 14 consecutive days; behavioral testing after 7 or 14 days; brain tissue analysis after 14 days |
| Measures | stereotyped behavior, forced swimming test (FST), locomotor activity, open field test, immunoreactivity of GAD67, TH, and PPAR-γ |
| Topics | Esketamine Ketamine |
| Key points | Ketamine given for 14 days produced positive-like schizophrenia symptoms (increased grooming) at all doses tested (20-40 mg/kg) and negative-like symptoms (increased forced-swim immobility) only at 30 mg/kg, without altering locomotor activity. No significant changes in GAD67, TH, or PPAR-γ immunoreactivity were observed, but these proteins correlated with specific behavioral measures, leading the authors to propose that the behavioral effects may depend on their modulatory roles. |
Abstract
Schizophrenia is a chronic, debilitating mental illness that has not yet been completely understood. In this study, we aimed to investigate the effects of different doses of ketamine, a non-competitive NMDA receptor antagonist, on the positive- and negative-like symptoms of schizophrenia. We also explored whether these effects are related to changes in the immunoreactivity of GAD67, TH, and PPAR-γ in brain structures. To conduct the study, male mice received ketamine (20-40 mg/kg) or its vehicle (0.9 % NaCl) intraperitoneally for 14 consecutive days. We quantified stereotyped behavior, the time of immobility in the forced swimming test (FST), and locomotor activity after 7 or 14 days. In addition, we performed ex vivo analysis of the immunoreactivity of GAD, TH, and PPAR-γ, in brain tissues after 14 days. The results showed that ketamine administration for 14 days increased the grooming time in the nose region at all tested doses. It also increased immobility in the FST at 30 mg/kg doses and decreased the number of rearing cycles during stereotyped behavior at 40 mg/kg. These behavioral effects were not associated with changes in locomotor activity. We did not observe any significant alterations regarding the immunoreactivity of brain proteins. However, we found that GAD and TH were positively correlated with the number of rearing during the stereotyped behavior at doses of 20 and 30 mg/kg ketamine, respectively. GAD was positively correlated with the number of rearing in the open field test at a dose of 20 mg/kg. TH was inversely correlated with immobility time in the FST at a dose of 30 mg/kg. PPAR-γ was inversely correlated with the number of bouts of stereotyped behavior at a dose of 40 mg/kg of ketamine. In conclusion, the behavioral alterations induced by ketamine in positive-like symptoms were reproduced with all doses tested and appear to depend on the modulatory effects of TH, GAD, and PPAR-γ. Conversely, negative-like symptoms were associated with a specific dose of ketamine.
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 |
Citations in the library
Cited by 5
- Effects of association between resveratrol and ketamine on behavioral and biochemical analysis in mice. Journal of Neural Transmission August 1, 2024
- Effects of acute and chronic ketamine administration on spontaneous and evoked brain activity. Brain Research 2025
- Ketamine Alters Specific Gene Expression Profiles by Transcriptome-Wide Responses in a Ketamine-Induced Schizophrenia-Like Mouse Model. Molecular Neurobiology February 24, 2025
- Investigating the effects of chlorogenic acid on novel object recognition memory impairment, hyperlocomotion, and prefrontal BDNF expression in a sub-chronic ketamine-induced schizophrenia-like rat model IBRO Neuroscience Reports July 24, 2026
- Ketamine impairs the performance of male mice in novel recognition object test and reduces the immunoreactivity of GAD67 in the hippocampus: Role of pioglitazone. Pharmacology, Biochemistry, and Behavior February 1, 2025
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and 6 more in the library