Psychedelic-like effects induced by 2,5-dimethoxy-4-iodoamphetamine, lysergic acid diethylamide, and psilocybin in male and female C57BL/6J mice.
Shelby A. McGriff, Jacquelin C Hecker, Alexander D. Maitland, John S. Partilla, Michael H. Baumann, Grant C. Glatfelter
Psychopharmacology May 17, 2025 DOI: 10.1007/s00213-025-06795-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Male and female C57BL/6J mice |
| Interventions | DOI LSD psilocybin |
| Dose | DOI 0.03-10 mg/kg, LSD 0.003-1 mg/kg, psilocybin 0.03-10 mg/kg |
| Duration | Acute effects |
| Topics | LSD Psilocybin |
| Keywords | 5-ht2a Head twitch response Mice Psychedelics hallucinogens Entheogens Psychoactive drugs Sexual dimorphism Neuroscience brain research Neurobiology Neural activity |
| Citations | 12 |
| Key findings | No substantial sex differences in potency to induce head twitch responses were found for DOI, LSD, and psilocybin in C57BL/6J mice, but females uniformly displayed more HTRs at high doses. |
Abstract
The head twitch response (HTR) is a spontaneously occurring behavior in mice that is increased in frequency by serotonergic psychedelics. The mouse HTR is often used as a proxy for psychedelic-like drug effects, but limited information is available about sex differences in HTRs evoked by various classes of psychedelics (i.e., phenethylamines, lysergamides, tryptamines). To examine potential sex differences in responsiveness to structurally-distinct psychedelics, acute effects of subcutaneous 2,5-dimethoxy-4-iodo-amphetamine (DOI, 0.03-10 mg/kg), lysergic acid diethylamide (LSD, 0.003-1 mg/kg), and 4-phosphoryloxy-N,N-dimethyltryptamine (psilocybin, 0.03-10 mg/kg) on HTRs were compared in male and female C57BL/6J mice. For comparison, effects of the drugs on locomotor activity and body temperature were also determined. Drug potencies for inducing HTRs were similar in males and females for all drugs, with only LSD exhibiting detectable differences due to increased maximal counts in females. Importantly, the maximum number of HTRs observed for all drugs was higher in females, with significant differences between sexes for DOI and LSD. Dose x sex interactions for the dose-response data were statistically significant for psilocybin and LSD, with females displaying more HTRs after the highest or peak doses of all drugs. The acute effects of drugs on locomotion and temperature varied by drug, but were similar in both sexes. The present results overall show no substantial sex differences in the potencies to induce HTRs for DOI, LSD, and psilocybin in C57BL/6J mice. However, females uniformly displayed more HTRs at high doses administered across chemotypes. The results further suggest that commonly used doses of psychedelics induce comparable psychedelic-like effects in male and female C57BL/6J mice, but modest differences may emerge at high doses.