Acute DOI treatment evokes dose and species-dependent locomotor effects on the elevated plus maze.
Praachi Tiwari, Vidita A Vaidya
Progress in Neuro-Psychopharmacology and Biological Psychiatry December 20, 2025 DOI: 10.1016/j.pnpbp.2025.111558 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study Peer reviewed |
|---|---|
| Population | Sprague-Dawley rats, 129S6/SvEv mice, C57BL/6J mice, and 5-HT2A receptor knockout mice |
| Intervention | DOI |
| Dose | 1 mg/kg |
| Topics | Anxiety |
| Keywords | Locomotion Mouse strain Psychedelic Serotonin 2a receptor |
| Key findings | DOI alters locomotor activity in a dose-dependent manner with species- and strain-specific differences, and these changes are mediated by the serotonin 2A receptor. |
Abstract
Recent evidence suggests that psychedelics hold promise in treating a range of neuropsychiatric disorders, highlighting the need to better understand their broader behavioral effects. Many animal-based behavioral assays related to mood, like anxiety and despair-like behavior, highly depend on locomotor activity. However, the influence of psychedelics on movement, especially in emotionally salient contexts, remains underexplored. While general locomotor activity can be monitored in the home cage, assessing movement in novel environments is critical for interpreting behaviors shaped by context and novelty. In this study, we examine the effects of the serotonergic psychedelic, DOI, on locomotor activity using the elevated plus maze (EPM), a conventionally used conflict-based anxiety maze. We find that DOI alters locomotor behavior in rats in a dose-dependent manner, and these changes are closely correlated with changes in anxiety-like behavior on the EPM. Notably, we observe species- and strain-specific differences in the DOI-evoked influence on spontaneous motor activity. While Sprague-Dawley rats and 129S6/SvEv mice exhibit reduced movement in response to 1 mg/kg DOI, C57BL/6J mice show increased movement at the same dose. The modulation of locomotor activity, like the observed anxiety-related effects, appears to be driven by the serotonin 2A receptor (5-HT2A R), as noted by the absence of DOI-evoked locomotor changes in 5-HT2A R knockout (KO) mice. These findings highlight the importance of considering the impact of serotonergic psychedelics on both spontaneous and context-dependent locomotion whilst interpreting mood-related behavioral responses in novelty-dependent, conflict-based approach-avoidance tasks.
Comparable studies
Other preclinical and animal studies on anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression Rats | 2020 | Preclinical study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study | |
| Chronic, Intermittent Microdoses of the Psychedelic N , N -Dimethyltryptamine (DMT) Produce Positive Effects on Mood and Anxiety in Rodents Male rats | 2019 | Animal study | |
| 3,4-Methylenedioxymethamphetamine facilitates fear extinction learning Mice | 2015 | Preclinical experimental study | |
| Repeated lysergic acid diethylamide (LSD) reverses stress-induced anxiety-like behavior, cortical synaptogenesis deficits and serotonergic neurotransmission decline Male mice exposed to chronic restraint stress | 2022 | Preclinical experimental study |
Citations in the library
Cited by 2
- Beyond head-twitch response: Acute psilocybin affects spontaneous behaviors in rats in a dose-dependent manner. Journal of Psychopharmacology August 25, 2026
- Classic psychedelics and autism spectrum disorder: preclinical evidence, mechanistic insights and unresolved challenges. Neuroscience & Biobehavioral Reviews August 1, 2026
Cites 18
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and 13 more in the library