To determine whether antibiotic-induced microbiome depletion influences baseline or 3,4-methylenedioxymethamphetamine (MDMA)-induced oxytocin signaling in rats. Male Wistar rats received broad-spectrum antibiotics (ABX) or water for 7 days, followed by a single oral administration of MDMA (30 mg/kg). Plasma oxytocin levels were measured by ELISA, and oxytocin-immunoreactivity in the...
), a combination of the muscarinic M1/M4 receptor agonist xanomeline and the peripherally restricted antagonist trospium, effectively reduces psychosis but is associated with gastrointestinal adverse effects. Here, we tested whether KarXT reverses phencyclidine (PCP)-induced cognitive deficits through microbiota-associated mechanisms in adult male mice. Mice received saline or PCP (10...
3,4-Methylenedioxymethamphetamine (MDMA) is widely used recreationally but also modulates serotonergic signaling in the gut, potentially influencing the microbiota. Because low bone mineral density (BMD) is common in depression and other psychiatric disorders, we tested whether repeated, intermittent MDMA attenuates BMD loss in ovariectomized (OVX) mice. OVX mice received MDMA (10 mg/kg) three...
Demyelination, defined as the loss of myelin sheaths around neuronal axons, is increasingly recognized as a key factor in a broad range of psychiatric and neurological disorders, including schizophrenia, major depressive disorder, bipolar disorder, post-traumatic stress disorder, autism spectrum disorder, substance use disorders, Alzheimer's disease, Parkinson's disease, and multiple sclerosis....
3,4-Methylenedioxymethamphetamine (MDMA) is a widely recognized entactogen frequently used recreationally. It is known for its interaction with the serotonin and oxytocin systems, which underlie its entactogenic effects in humans. Recently, we demonstrated that the gut-brain axis, mediated by the subdiaphragmatic vagus nerve, contributes to MDMA-induced resilience enhancement in rodents. This...
3,4-Methylenedioxymethamphetamine (MDMA), commonly known as a recreational drug, may also offer therapeutic benefits for mental health. Population-based studies suggest that MDMA users have a lower risk of demyelinating diseases, such as depression. Given the role of the gut microbiota in mediating MDMA's effects, we hypothesized that MDMA might confer mental health benefits via the gut-brain...
Postoperative cognitive dysfunction (POCD) is characterized by a decline in cognitive functions, including memory, attention, and executive abilities, following surgery, with no effective therapeutic drugs currently available. Arketamine, the (R)-enantiomer of ketamine, has shown promise in mitigating cognitive deficits in animal models. In this study, we investigated whether arketamine could...
3,4-Methylenedioxymethamphetamine (MDMA; Ecstasy) is a widely abused recreational drug that has also gained interest for potential clinical applications in mental health. With the growing recognition of gut microbiota's role in mental health, this study examined whether repeated oral MDMA administration could affect gut microbiota in the small intestine, cecum, and colon of male rats. Repeated...
Chronic restrain stress (CRS) induces depression-like behaviors and demyelination in the brain; however, the relationship between these depression-like behaviors and demyelination remains unclear. Arketamine, the (R)-enantiomer of ketamine, has shown rapid antidepressant-like effects in CRS-exposed mice. We examined whether arketamine can improve both depression-like behaviors and demyelination...
The novel antidepressant arketamine, the (R)-enantiomer of ketamine, has been shown to ameliorate demyelination and facilitate remyelination in the brains of cuprizone (CPZ)-treated mice. However, the mechanisms behind its effects remain unclear. Given the role of transforming growth factor β1 (TGF-β1) in arketamine's antidepressant-like effects, we examined whether TGF-β1 also plays a role in...
Arketamine, the (R)-enantiomer of ketamine, exhibits both therapeutic and sustained prophylactic effects in an inflammation-driven model of depression, although the precise mechanisms remain elusive. Given the involvement of γδ T cells in inflammatory processes, this study explored their role in the effects of arketamine. To assess therapeutic outcomes, mice received lipopolysaccharide (LPS:1.0...
The gut-brain axis, which includes gut microbiota and microbiome-derived metabolites, might be implicated in depression. We reported the sustained prophylactic effects of a new antidepressant arketamine in chronic restrain stress (CRS) model of depression. In this study, we investigated the role of gut-brain axis on the prophylactic effects of arketamine in the CRS (7 days) model. Pretreatment...
Anesthetic ketamine and classical psychedelics that act as 5-hydroxytryptamine-2A receptor (5-HT2AR) agonists demonstrated rapid and sustained antidepressant actions in patients with treatment-resistant depression. The new antidepressant arketamine is reported to cause long-lasting prophylactic effects in lipopolysaccharide (LPS)-treated mice and mice exposed to chronic restrain stress (CRS)....