Beyond head-twitch response: Acute psilocybin affects spontaneous behaviors in rats in a dose-dependent manner.
Praachi Tiwari, Bryan W. Jenkins, Catherine F Moore, Hudson Zhou, Tylaah George, David B. Yaden, Elise M Weerts
Journal of Psychopharmacology August 25, 2026 DOI: 10.1177/02698811261478600 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Male and female Sprague-Dawley rats |
| Intervention | Psilocybin |
| Dose | 0.5, 1, 1.5 mg/kg, i.p. |
| Topics | Psilocybin |
| Keywords | Sprague-dawley rats Dose-curve Pattern Psychedelic |
| Key findings | Psilocybin produced a bell-shaped dose-response for HTR/WDS, linearly increased immobility, decreased rearing and grooming even at low doses, decreased sniffing/digging only at higher doses, and variably increased circling across doses and sexes, with some behaviors correlated in a dose-dependent manner. |
Abstract
Psychedelics have emerged as promising pharmacological agents for treating a range of neuropsychiatric disorders. While preclinical studies have provided valuable insight into the neural mechanisms underlying their effects, systematic characterization of psychedelic effects on inherent spontaneous behaviors in animal models remains limited. In the current study, male and female Sprague-Dawley rats were administered psilocybin (0.5, 1, 1.5 mg/kg, i.p.) or its vehicle (saline). Behaviors were video recorded for subsequent analysis. In addition to the widely studied head-twitch response and wet dog shakes (HTR/WDS), five additional spontaneous behaviors that were modulated by psilocybin (immobility, rearing, grooming, sniffing/digging, and circling) were assessed. Assessed behaviors showed distinct dose-response profiles in both sexes. When compared to saline, psilocybin elicited HTR/WDS following a bell-shaped curve, while immobility increased linearly, with dose. Rearing and grooming decreased markedly even at low doses, sniffing/digging declined only at higher doses, and circling increased variably across doses for each sex. Furthermore, some behaviors were correlated in a dose-dependent manner. Together, our findings highlight a broader range of behaviors influenced by psilocybin beyond HTR and provide a framework for identifying its neurobehavioral effects in Sprague-Dawley rats within a widely used physiologically relevant dose range.
Comparable studies
Other preclinical and animal studies on psilocybin, 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 | |
| Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Mice | 2021 | Experimental study | |
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study |
Citations in the library
Cites 33
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
- Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Neuropsychopharmacology January 26, 2019
- Activation of Serotonin 2A Receptors Underlies the Psilocybin-Induced Effects on Oscillations, N170 Visual-Evoked Potentials, and Visual Hallucinations Journal of Neuroscience June 19, 2013
- The neural basis of psychedelic action. Nature Neuroscience October 24, 2022
- Differential contributions of serotonin receptors to the behavioral effects of indoleamine hallucinogens in mice Journal of Psychopharmacology December 8, 2010
and 28 more in the library