Ketamine Alters Specific Gene Expression Profiles by Transcriptome-Wide Responses in a Ketamine-Induced Schizophrenia-Like Mouse Model.
Zhe Du, Xiu-Mei Zhu, Peng Lv, Ying Pan, Xi-Kai Hou, Ang Li, Dong Zhao, Jia-Xin Xing, Jun Yao
Molecular Neurobiology February 24, 2025 DOI: 10.1007/s12035-025-04789-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | ketamine |
| Duration | Two weeks after ketamine administration |
| Topics | Ketamine Esketamine |
| Keywords | Rgs4 Transcriptome Ketamine abuse Psychiatric disorders Neuroscience research Molecular biology Gene expression |
| Citations | 2 |
| Key findings | Blocking Drd1 activity mitigated ketamine-induced schizophrenia-like behaviors, and Gnai3 and eotaxin-2 may serve as potential peripheral biomarkers for ketamine abuse in mice. |
Abstract
Psychotic disorder is a significant consequence of ketamine abuse. However, the molecular mechanisms and biomarkers for this psychotic disorder and associated long-term cognitive impairment remain unclear. To investigate the behavioral changes and comprehensive gene expression alterations in mice following ketamine administration, we employed behavioral testing and RNA sequencing (RNA-seq). We further examined the role of dopamine D1 receptor (Drd1) activity in mediating ketamine-induced psychotic-like behavior and its impact on the transcriptome in these mice. Our findings indicated that blocking Drd1 activity with an antagonist mitigated ketamine-induced schizophrenia-like behaviors, while activating Drd1 with an agonist partially replicated these symptoms. Transcriptome analysis of the mouse hippocampus using RNA-seq revealed an enrichment of differentially expressed genes implicated in the GTPase activation pathway. Specifically, both Rgs4 and Gnai3 were involved in ketamine-induced psychiatric effects. Furthermore, we observed that the mRNA expression of Gnai3 was decreased in peripheral blood and the serum levels of eotaxin-2 were elevated two weeks after ketamine administration. These changes suggest that Gnai3 and eotaxin-2 may serve as potential biomarkers for ketamine abuse. These results demonstrate the crucial role of Drd1 activity in a mouse model of ketamine-induced schizophrenia-like disorder. The altered expression of Gnai3 in peripheral blood and the elevated levels of cytokine eotaxin-2 in serum indicate their potential as peripheral blood biomarkers for ketamine abuse in mice.
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 11
- Ketamine Rapidly Enhances Glutamate-Evoked Dendritic Spinogenesis in Medial Prefrontal Cortex Through Dopaminergic Mechanisms. Biological Psychiatry January 8, 2021
- Ketamine exerts its sustained antidepressant effects via cell-type-specific regulation of Kcnq2. Neuron May 1, 2022
- The clinical toxicology of ketamine Clinical Toxicology June 2, 2023
- Influence of the dose of ketamine used on schizophrenia-like symptoms in mice: A correlation study with TH, GAD67, and PPAR-γ. Pharmacology, Biochemistry, and Behavior October 1, 2023
- Association between peripheral biomarkers and clinical response to IV ketamine for unipolar treatment-resistant depression: An open label study. Journal of Affective Disorders September 1, 2022
and 6 more in the library