Molecular Neurobiology
February 24, 2025
Zhe Du, Xiu-Mei Zhu, Peng Lv et al.
2 citations
Blocking dopamine D1 receptor (Drd1) activity with an antagonist reduced ketamine-induced schizophrenia-like behaviors in mice, while activating Drd1 with an agonist partly reproduced those symptoms. Transcriptome analysis of the mouse hippocampus identified changes in genes involved in the GTPase activation pathway, including Rgs4 and Gnai3. Two weeks after ketamine administration, Gnai3 mRNA expression decreased in peripheral blood and serum levels of eotaxin-2 increased. These molecular changes suggest Gnai3 and eotaxin-2 may serve as potential peripheral biomarkers for ketamine abuse. The findings demonstrate Drd1 activity's crucial role in ketamine-induced psychotic-like disorder in a mouse model.
Behavioral and brain functions : BBF
June 25, 2026
Xiu-Mei Zhu, Yang Li, Wenrui Liu et al.
Ketamine triggers a rapid increase in histone H3 Ser10 phosphorylation in mouse hippocampal neurons and in the mouse hippocampus, an effect driven by JNK activation. Blocking JNK with SP600125 reversed this epigenetic change and reduced ketamine-induced hyperlocomotion and cognitive deficits. Multi-omics analysis 30 minutes after ketamine identified 262 differentially expressed genes, including MAP3K9, enriched in MAPK signaling and neuroactive ligand-receptor pathways, and 165 differentially accessible chromatin regions, with CTCF as a potential regulator. The findings suggest that JNK-mediated H3S10 phosphorylation links ketamine exposure to psychosis-like behaviors, offering a mechanistic connection between stress-sensitive signaling, rapid chromatin remodeling, and transcriptional reprogramming.
Cell Biology and Toxicology
January 30, 2026
Jia-Yi Wei, Peng Lv, Jiayu Zhang et al.
Repeated ketamine exposure over seven days causes anxiety-like and depressive-like behaviors along with cognitive deficits in mice. The dopamine receptor DRD1 plays a key role in these effects: activating DRD1 produces anxiety-like behavior similar to ketamine and worsens ketamine's effects, while blocking DRD1 partially reduces anxiety but worsens depression. Ketamine triggers apoptosis (cell death) in HT22 cells by suppressing Akt/Gsk3β phosphorylation through DRD1. In mice, ketamine promotes neuronal apoptosis in the hippocampus and prefrontal cortex; blocking DRD1 partially reduces this apoptosis, but knocking down DRD1 in neurons unexpectedly increases both apoptosis and anxiety-like behavior.
Cell Biology and Toxicology
November 25, 2025
Peng Lv, Jiayu Zhang, Jia-Yi Wei et al.
Repeated ketamine exposure can trigger psychotic-like behaviors and cognitive deficits through a specific molecular pathway involving the dopamine receptor DRD1. The DRD1–DARPP-32–Histone H3 signaling cascade mediates transcriptional abnormalities and impairs neurogenesis in the hippocampus. Blocking DRD1 alleviated these effects, while activating it partially reproduced ketamine-like symptoms. In cellular and mouse models, ketamine increased phosphorylation of DARPP-32 at Thr34, promoting its nuclear accumulation and leading to histone H3 phosphorylation. This altered gene expression and reduced the generation of new neurons and neural stem cells in the dentate gyrus, while increasing astrocyte numbers. The findings suggest a key mechanism underlying ketamine-induced schizophrenia-like symptoms.
Nature Communications
June 5, 2023
Ang Li, Haiyang Liu, Xu Lei et al.
Consciousness is linked to how neural activity shifts along a unimodal-transmodal cortical axis, a simple signature that is abnormally elevated under psychedelics and in psychosis. This hierarchical dynamic reflects changes in global brain integration and connectome diversity. Quasi-periodic patterns show hierarchical heterogeneity as spatiotemporally propagating waves tied to arousal, a pattern also seen in macaques. The spatial distribution of the principal cortical gradient aligns with genetic transcription of the histaminergic system and functional connectome mapping of the tuberomammillary nucleus, which promotes wakefulness. Combining behavioral, neuroimaging, electrophysiological, and transcriptomic evidence, the authors propose that global consciousness is supported by efficient hierarchical processing along a low-dimensional macroscale gradient.