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.