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Rearing behaviour in the mouse behavioural pattern monitor distinguishes the effects of psychedelics from those of lisuride and TBG

Yahong Chen, Junhong Liu, Yishan Yao, Haitao Yan, Ruibin Su

Frontiers in Pharmacology February 16, 2023 DOI: 10.3389/fphar.2023.1021729 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Preclinical experimental study Peer reviewed
Population Mice
Interventions DOM mescaline psilocin 25CN-NBOH TBG lisuride M100907
Topics Mescaline Serotonin
Keywords Hallucinogen Lisuride Locomotor activity Pharmacology Partial agonist Metergoline
Citations 19
Key findings Increased rearing in mice may differentiate hallucinogenic from nonhallucinogenic 5-HT2A agonists, and DOM-elicited increases in rearing are mediated by the 5-HT2A receptor.

Abstract

Psychedelics alter consciousness and may have potential for drug development. As psychedelics are likely therapeutically active, it is important to study their effects and mechanisms using preclinical models. Here, we examined the effects of phenylalkylamine and indoleamine psychedelics on locomotor activity and exploratory behaviour using the mouse Behavioural Pattern Monitor (BPM). DOM, mescaline, and psilocin reduced locomotor activity at high doses and influenced rearings, an exploratory behaviour, in a characteristic inverted U-shaped dose-response function. Pretreatment with the selective 5-HT 2A antagonist M100907 reversed the drug-induced alterations in locomotor activity, rearings, and jumps after systemic administration of DOM at low doses. However, holepoking at the full range of doses tested was not blocked by M100907. Administration of the hallucinogenic 5-HT 2A agonist 25CN-NBOH induced striking similarities in response to that to psychedelics; these alterations were significantly diminished by M100907, whereas the putatively non-hallucinogenic 5-HT 2A agonist TBG did not affect locomotor activity, rearings, or jumps at the most effective doses. The nonhallucinogenic 5-HT 2A agonist lisuride failed to increase rearing. The results of these experiments provide strong evidence that DOM-elicited increases in rearing are due to mediation by the 5-HT 2A receptor. Finally, discriminant analysis was able to distinguish all four psychedelics from lisuride and TBG based on behavioural performance alone. Thus, increased rearing in mice could provide additional evidence of behavioural differences between hallucinogenic and nonhallucinogenic 5-HT 2A agonists.

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

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Cites 31

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Related reading

Explore topics

Mescaline Serotonin Altered states of consciousness Microdosing Philosophy of mind Psilocybin