Neuropharmacology
September 1, 2022
Hao-Ming Hua, Chao Huang, Hanyu Liu et al.
35 citations
Ketamine's rapid antidepressant effects, a major advance in depression treatment, may involve the gut-brain axis. This review examines how ketamine and its metabolites interact with the gut microbiome and microbiota-derived molecules. The proposed mechanisms include modulation of the stress response, promotion of brain-derived neurotrophic factor (BDNF)-mediated neurogenesis, anti-inflammatory effects, and regulation of neurotransmitters. However, the exact mechanisms remain unclear.
Translational Psychiatry
September 3, 2021
Chao Huang, Yuanyuan Wang, Zifeng Wu et al.
29 citations
Ketamine acts as a rapid and long-lasting antidepressant, but its molecular mechanisms are unclear. In mice subjected to chronic social stress, microRNA miR-98-5p was downregulated in the prefrontal cortex and hippocampus. Overexpressing miR-98-5p with an agonist alleviated depression-like behaviors. Ketamine administration upregulated miR-98-5p, and inhibiting it with an antagonist blocked ketamine's antidepressant effect. This suggests a novel molecular mechanism for ketamine's action and that targeting miR-98-5p could be beneficial for depression treatment.
Frontiers in Neuroscience
May 23, 2023
Junhong Liu, Yuanyuan Wang, Ke Xia et al.
17 citations
Psilocybin, the hallucinogenic compound in magic mushrooms, activates brain regions and increases functional connectivity in rats, similar to its effects in humans. Ten minutes after injection (2.0 mg/kg), positive brain activity appeared in the frontal, temporal, and parietal cortex, hippocampus, and striatum. Connectivity increased among regions including the cingulate cortex, dorsal striatum, prelimbic, and limbic areas. Psilocybin also raised levels of EGR1, a protein linked to depressive symptoms, throughout the brain, indicating widespread activation. These findings suggest the hyperactive state may underlie psilocybin's pharmacological effects.
British journal of pharmacology
July 1, 2026
Yuanyuan Wang, Yishan Yao, Ruibin Su et al.
1 citation
The psychedelic compound 4-acetoxy-N,N-dimethyltryptamine (4-AcO-DMT) suppresses innate fear responses in rats by activating 5-HT₂A receptors, which recruit vasoactive intestinal polypeptide (VIP) interneurons in the prelimbic cortex. In behavioral experiments, 4-AcO-DMT reduced predator odor-evoked 22-kHz ultrasonic vocalizations, a fear-related response, through this specific cortical microcircuit mechanism. Chemogenetic activation of VIP interneurons abolished the fear-suppressing effect, confirming their role. The findings advance understanding of how serotonergic psychedelics modulate fear circuits at a neurobiological level, with potential implications for treating fear-related psychiatric disorders like phobias and anxiety.
Neuroscience
March 5, 2025
Hanyu Liu, Siqi Yang, Qi Zhang et al.
Opioid-induced hyperalgesia (OIH) is a complication of pain treatment where opioids paradoxically increase pain sensitivity. Using a mouse model, about 60% of mice developed OIH after three days of morphine, shown by abnormal movement and anxiety-like behaviors. Mice whose gut microbiota were eliminated with antibiotics did not develop hyperalgesia, but those receiving fecal transplants from OIH mice did. S-ketamine, but not R-ketamine, prevented OIH. Gut microbiota analysis revealed increased Enterobacteriaceae in OIH-susceptible mice, which decreased after S-ketamine treatment. The findings suggest S-ketamine alleviates morphine-induced OIH by reducing gut Enterobacteriaceae levels.