2,5-dimethoxy-4-methylamphetamine (DOM)-induced Gait Alterations in Mice: Dissecting the Role of 5-HT2A/2C Receptor-mediated Mechanisms.
Bin Li, Shanshan Jiang, Yi-shan Yao, Gang Yu, Rui-Bin Su
European Journal of Pharmacology September 15, 2025 DOI: 10.1016/j.ejphar.2025.178170 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | C57BL/6J mice |
| Interventions | MDL100907 SB242084 |
| Dose | 0.3-3 mg/kg DOM; 10 mg/kg DOM; 0.1 mg/kg MDL100907; 1 mg/kg SB242084 |
| Topics | Serotonin |
| Key points | DOM at 0.3-3 mg/kg increased locomotor velocity in mice by increasing stride frequency and length and reducing stance duration, while 10 mg/kg suppressed voluntary locomotion, reversible by 5-HT2C antagonism. The authors report that DOM's gait effects were primarily mediated through 5-HT2A receptors, since 0.1 mg/kg MDL100907 but not 1 mg/kg SB242084 normalized the alterations. |
Abstract
Psychedelics have demonstrated significant therapeutic potential in treating various psychiatric disorders; however, their effects on motor function remain poorly understood. This study investigated the impact of 2,5-dimethoxy-4-methylamphetamine (DOM), a classical phenethylamine psychedelic agent, on gait parameters in C57BL/6J mice using an active gait monitoring system. We found that 0.3-3 mg/kg DOM significantly increased locomotor velocity by enhancing stride frequency and length while reducing stance duration. These effects were accompanied by decreased plantar pressure and more concentrated paw placement patterns. High-dose DOM (10 mg/kg) suppressed voluntary locomotion, which was reversible by 5-HT2C receptor antagonism. Pharmacological studies using subtype-selective serotonin receptor antagonists revealed that DOM's effects on gait parameters were primarily mediated through 5-HT2A receptors. Pretreatment with 0.1 mg/kg MDL100907, but not 1 mg/kg SB242084, normalized DOM-induced gait alterations. Moreover, the antagonism of 5-HT2A or 5-HT2C receptor alone modified baseline gait parameters, suggesting the complex serotonergic regulation of locomotor function. These findings reveal alterations in fine gait parameters following DOM administration, expanding our understanding of the complicated effects of psychedelics.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cites 13
- Psychedelic Psychiatry's Brave New World. Cell April 1, 2020
- Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. Neuropharmacology May 1, 2020
- Effects of psilocybin on time perception and temporal control of behaviour in humans Journal of Psychopharmacology May 20, 2006
- Looking for the Self: Phenomenology, Neurophysiology and Philosophical Significance of Drug-induced Ego Dissolution Frontiers in Human Neuroscience May 23, 2017
- Classical Psychedelics as Therapeutics in Psychiatry – Current Clinical Evidence and Potential Therapeutic Mechanisms in Substance Use and Mood Disorders Pharmacopsychiatry January 20, 2021
and 8 more in the library