Ketamine impairs the performance of male mice in novel recognition object test and reduces the immunoreactivity of GAD67 in the hippocampus: Role of pioglitazone.
Talita Rodrigues, Getulio Nicola Bressan, Patrícia Zorzi Juliani, Maria Eduarda Brandli da Silva, Roselei Fachinetto
Pharmacology, Biochemistry, and Behavior February 1, 2025 DOI: 10.1016/j.pbb.2024.173950 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experiment Peer reviewed |
|---|---|
| Population | Male mice |
| Interventions | ketamine pioglitazone |
| Dose | 30 mg/kg ketamine, 3 or 9 mg/kg pioglitazone |
| Duration | 14 consecutive days of ketamine administration; pioglitazone from day 8 to day 14 |
| Topics | Esketamine Ketamine |
| Keywords | Animal behavior Monoamine oxidase Open field Social interaction Stereotypy Tyrosine hydroxylase Psychopharmacology Behavioral research Cognitive function Drug interactions |
| Key findings | Pioglitazone reversed ketamine-induced deficits in novel object recognition and restored hippocampal GAD67 immunoreactivity, indicating a potential role in treating cognitive symptoms of schizophrenia. |
Abstract
Schizophrenia is a mental disorder characterized by positive, negative, and cognitive symptoms which is treated with antipsychotics. However, these drugs present several side effects and, some schizophrenia symptoms, like cognitive, are difficult to treat. The peroxisome proliferator-activated receptors-gamma (PPAR-γ) are expressed in dopaminergic neurons of the midbrain participating in the modulation of dopamine-mediated behavior . We investigated the effects of pioglitazone, an agonist of PPAR-γ, on the behavioral alterations induced by ketamine and, whether alterations in monoamine oxidase (MAO) activity, glutamic acid decarboxylase (GAD67), PPAR-γ or tyrosine hydroxylase (TH) immunoreactivity in brain tissues are involved in these effects. Male mice received ketamine (30 mg/kg), intraperitoneally, for 14 consecutive days, and pioglitazone (3 or 9 mg/kg), by gavage (day 8 up to day 14). Ketamine decreased nail-biting increasing the time exploring the center of the open field on day 8 and the number of rearing evaluated 30 min after its administration on day 14. Furthermore, ketamine decreased the percentage of investigation in the NOR test and the immunoreactivity of GAD67 in the hippocampus. No significant changes were found in other behavioral and biochemical tests. Pioglitazone attenuated the effects of ketamine on rearing and GAD67 immunoreactivity in the hippocampus, recovering the ketamine effects on NOR test. At a dose of 9 mg/kg, pioglitazone alone reduced the immunoreactivity of GAD67 in the hippocampus. Pioglitazone at both doses recovered the cognitive symptoms induced by ketamine an effect that seems to involve the modulation of GAD67 immunoreactivity in the hippocampus. In conclusion, pioglitazone improved the effects of ketamine on the NOR test which was, at least in part, associated with the modulation of GAD67 immunoreactivity in the hippocampus suggesting its beneficial role in cognitive symptoms.
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
Cites 12
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Reviewing the ketamine model for schizophrenia Journal of Psychopharmacology November 20, 2013
- Beyond the dopamine hypothesis of schizophrenia to three neural networks of psychosis: dopamine, serotonin, and glutamate CNS Spectrums June 1, 2018
- Is the Acute NMDA Receptor Hypofunction a Valid Model of Schizophrenia? Schizophrenia Bulletin September 28, 2011
and 7 more in the library