Mescaline-induced behavioral alterations are mediated by 5-HT2A and 5-HT2C receptors in rats.
Lucie Olejníková-Ladislavová, Michaela Fujáková-Lipski, Klára Šíchová, Hynek Danda, Kateřina Syrová, Jiří Horáček, Tomáš Páleníček
Pharmacology, Biochemistry, and Behavior December 1, 2024 DOI: 10.1016/j.pbb.2024.173903 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Adult male Wistar rats |
| Interventions | Mescaline 5-HT2A antagonist 5-HT2C antagonist |
| Dose | 10, 20, and 100 mg/kg |
| Topics | Mescaline Serotonin |
| Keywords | Psychedelics hallucinogens Locomotor activity Sensorimotor gating Psychedelic compounds Psychoactive substances Neuroscience brain chemistry Neurotransmitters Neural mechanisms Serotonin receptors 5-ht2a |
| Citations | 5 |
| Key findings | Mescaline-induced hyperlocomotion and sensorimotor gating deficits in rats are primarily mediated by the 5-HT2A receptor subtype, with a lesser contribution from the 5-HT2C receptor. |
Abstract
Mescaline is a classical psychedelic compound with a phenylethylamine structure that primarily acts on serotonin 5-HT2A/C receptors, but also binds to 5-HT1A and 5-HT2B receptors. Despite being the first psychedelic ever isolated and synthesized, the precise role of different serotonin receptor subtypes in its behavioral pharmacology is not fully understood. In this study, we aimed to investigate how selective antagonists of 5-HT2A, 5-HT2B, 5-HT2C, and 5-HT1A receptors affect the behavioral changes induced by subcutaneous administration of mescaline (at doses of 10, 20, and 100 mg/kg) in rats. We used adult male Wistar rats in all our experiments. We evaluated locomotor activity using the open field test, and assessed sensorimotor gating deficits by measuring prepulse inhibition (PPI) of acoustic startle reaction (ASR). While the highest dose of mescaline induced hyperlocomotion (p < 0.001), which almost all the other antagonists reversed (p < 0.05-0.001), the PPI deficits were selectively normalized by the 5-HT2A antagonist (p < 0.05-0.01). The 5-HT2C antagonist partially reversed the small PPI deficit induced by lower doses of mescaline (p = 0.0017). Our findings suggest that mescaline-induced changes in behavior are primarily mediated by the 5-HT2A receptor subtype, with less pronounced contributions from the 5-HT2C receptor. The other antagonists had limited effects.
Comparable studies
Other preclinical and animal studies on mescaline, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| 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 | |
| Brain mechanisms of hallucinogens and entactogens Humans and rats | 2001 | Review | |
| Effects of hallucinogenic agents mescaline and phencyclidine on zebrafish behavior and physiology Zebrafish (Danio rerio) | 2012 | Experimental study | |
| Lysergic Acid Diethylamide- and Mescaline-Induced Attenuation of the Effect of Punishment in the Rat Rats | 1976 | Experimental study | |
| Dihydrobenzofuran Analogues of Hallucinogens. 3. Models of 4-Substituted (2,5-Dimethoxyphenyl)alkylamine Derivatives with Rigidified Methoxy Groups Rats (trained to discriminate saline from LSD tartrate) and rat cortical and... | 1996 | In vivo drug discrimination assay and in vitro radioligand binding assay |
Citations in the library
Cited by 5
- The polypharmacology of psychedelics reveals multiple targets for potential therapeutics. Neuron July 15, 2025
- The effect of psychedelic microdosing on animal behavior: A review with recommendations for the field Neuroscience & Biobehavioral Reviews May 9, 2025
- Short- and Long-Acting Psychedelics: Structure-Activity Relationships, Pharmacology, and Implications for Neuropsychiatric Therapeutics. ACS Chemical Neuroscience June 17, 2026
- Mescaline Alters Cerebellar Function, Global Connectivity, and Frequency-Selective Acoustic Gating: A BOLD fMRI Study in Awake Rats. Neuroscience Bulletin May 21, 2026
- Predictors of the Effectiveness of Psychedelics in Treating Depression—A Scoping Review International Journal of Molecular Sciences February 26, 2026
Cites 22
- Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. European Neuropsychopharmacology May 20, 2016
- Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs). Neuropharmacology December 1, 2015
- Mescaline-induced psychopathological, neuropsychological, and neurometabolic effects in normal subjects: experimental psychosis as a tool for psychiatric research. Biological Psychiatry December 1, 1992
- The serotonin 2C receptor potently modulates the head-twitch response in mice induced by a phenethylamine hallucinogen Psychopharmacology February 19, 2010
- 5HT-2 mediation of acute behavioral effects of hallucinogens in rats Psychopharmacology March 1, 1990
and 17 more in the library