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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) via OpenAlex

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
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.

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