Effects of the hallucinogenic drugs mescaline, phencyclidine and psilocybin on zebrafish behavior and physiology
Evan J. Kyzar, Christopher Collins, Jeremy Green, Siddharth Gaikwad, Andrew Roth, Louis Monnig, Mohamed El-Ounsi, Nicholas Capezio, Andrew J. Freeman, Ari Davis, Allan V. Kalueff
The FASEB Journal April 1, 2012 DOI: 10.1096/fasebj.26.1_supplement.1043.3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Zebrafish (Danio rerio) |
| Interventions | Mescaline Phencyclidine (PCP) Psilocybin |
| Dose | Mescaline 10–20 mg/L, PCP 1–3 mg/L, Psilocybin 0.5–3 mg/L |
| Topics | LSD Mescaline Psilocybin |
| Keywords | Hallucinogen Phencyclidine Pharmacology Zebrafish Psychotomimetic Danio Scratching Open field |
| Citations | 1 |
| Key findings | Mescaline and PCP produce distinct behavioral and physiological effects in zebrafish, whereas psilocybin is behaviorally inactive at the doses tested. |
Abstract
Mescaline, phencyclidine (PCP) and psilocybin are potent hallucinogenic drugs strongly affecting both human and animal behavior. However, these compounds have not been previously investigated in zebrafish (Danio rerio), rapidly gaining popularity as a model in psychopharmacology research. Here, we examine the effects of mescaline, PCP and psilocybin in multiple behavioral paradigms. Mescaline (10–20 mg/L) generally displayed an anxiolytic effect in the novel tank test, while PCP (1–3 mg/L) reduced freezing behavior and elicited a pattern of erratic swimming. Mescaline‐treated fish markedly increased shoaling behavior and altered movement patterns in the open field test. Additionally, mescaline and PCP disrupted normal zebrafish exploratory behavior, as assessed by ethograms. Psilocybin at doses tested (0.5–3 mg/L) was inactive in all of the behavioral tests. Interestingly, both psilocybin and PCP raised whole‐body cortisol levels without affecting brain c‐fos expression, and mescaline did not alter cortisol or c‐fos levels. Overall, this confirms the high sensitivity of zebrafish models to various hallucinogenic compounds with complex behavioral and physiological profiles. This study was supported by the National Institute on Drug Abuse (NIDA) R03 grant to AVK.
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 |