Ketamine enhances dopamine D1 receptor expression by modulating microRNAs in a ketamine-induced schizophrenia-like mouse model.
Xiaojiaoyang Li, Juanhan Yu, Xue Wu, Xiu-Mei Zhu, Peng Lv, Zhe Du, Yan Lü, Xu Wu, Jun Yao
Neurotoxicology and Teratology February 21, 2022 DOI: 10.1016/j.ntt.2022.107079 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Mice (C57BL/6J) and HT22 mouse hippocampal neuronal cells |
| Intervention | ketamine |
| Dose | high-dose ketamine |
| Duration | Seven consecutive days |
| Topics | Esketamine Ketamine |
| Key points | Ketamine induces schizophrenia-like behaviors in mice and upregulates DRD1 expression by inhibiting miR-15a-3p, miR-15b-3p, and miR-16-1-3p. |
Abstract
The abnormal expression of the dopamine D1 receptor (DRD1) may be associated with schizophrenia. MicroRNAs (miRNAs) can post-transcriptionally regulate DRD1 expression. Here, we established a ketamine-induced schizophrenia-like behavior mouse model and investigated the changes in miR-15a-3p, miR-15b-3p, miR-16-1-3p, and DRD1 in response to ketamine. Administration of high-dose ketamine for seven consecutive days to mice simulated the main symptoms of schizophrenia. The mice exhibited increasing excitability and autonomous activity and reduced learning and memory, including spatial memory. Moreover, ketamine decreased miR-15a-3p, miR-15b-3p, and miR-16-1-3p expression levels in the prefrontal cortex (PFC) and miR-16-1-3p expression in the hippocampus, whereas DRD1 expression increased in these brain regions. In HT22 mouse hippocampal neuronal cells, ketamine induced a dose-dependent increase of endogenous DRD1, which was partially attenuated by a combination of miR-15b-3p and miR-16-1-3p mimics. Indeed, the miR-15b-3p and miR-16-1-3p mimics could significantly inhibit endogenous DRD1expression. We identified +72 to +78 bp (TGCTGCT) of the DRD1 3'UTR as the core regulatory region recognized by the target miRNAs. In summary, we developed a ketamine-induced schizophrenia-like behavior mouse model and found that ketamine inhibited the levels of miR-15a-3p, miR-15b-3p, miR-16-1-3p and increased DRD1 expression 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
Cited by 7
- Ketamine and serotonergic psychedelics: An update on the mechanisms and biosignatures underlying rapid-acting antidepressant treatment Neuropharmacology January 13, 2023
- Epigenetic mechanisms of rapid-acting antidepressants Translational Psychiatry September 4, 2024
- Ketamine Alters Specific Gene Expression Profiles by Transcriptome-Wide Responses in a Ketamine-Induced Schizophrenia-Like Mouse Model. Molecular Neurobiology February 24, 2025
- Ketamine enhances histone H3 (Ser10) phosphorylation via JNK signaling and multi-omics profiling of the hippocampus in a psychotic-like mouse model. Behavioral and Brain Functions June 25, 2026
- Repeated 7-day exposure to ketamine induces anxiety-like behaviors and neuronal apoptosis in mice via DRD1-medicated inhibition of Akt/Gsk-3β phosphorylation. Cell Biology and Toxicology January 30, 2026
and 2 more in the library
Cites 5
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- Optogenetic stimulation of medial prefrontal cortex Drd1 neurons produces rapid and long-lasting antidepressant effects Nature Communications January 15, 2019
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