Investigating the role of 5-HT2A and 5-HT2C receptor activation in the effects of psilocybin, DOI, and citalopram on marble burying in mice
Anna U. Odland, Jesper L. Kristensen, Jesper T. Andreasen
Behavioural Brain Research December 28, 2020 DOI: 10.1016/j.bbr.2020.113093 via OpenAlex
Summary
AI-generated from the abstractPsychedelic drugs that activate the 5-HT2A receptor show promise for treating psychiatric disorders like obsessive-compulsive disorder. In a mouse model of compulsive-like behavior (the marble burying test), the 5-HT2A receptor antagonist M100907 blocked the effect of the psychedelic DOI, and the 5-HT2C receptor antagonist SB242084 blocked the effect of citalopram, but neither antagonist blocked the effect of psilocybin. This confirms 5-HT2A receptor activation as a mechanism for reducing compulsive-like digging and suggests that 5-HT2A and 5-HT2C receptors can work in parallel. The results with psilocybin indicate that a mechanism independent of 5-HT2 receptors also contributes to its effect on repetitive digging.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Female NMRI mice |
| Interventions | DOI psilocybin citalopram M100907 SB242084 |
| Topics | Psilocybin |
| Keywords | Citalopram Psychology Hallucinogen Pharmacology |
| Citations | 60 |
| Key finding | Psilocybin reduces compulsive-like digging in mice through a mechanism that is not blocked by 5-HT2A or 5-HT2C receptor antagonists, suggesting a 5-HT2 receptor-independent pathway. |
Abstract
Psychedelic drugs acting as 5-hydroxyptryptamine 2A receptor (5-HT2AR) agonists have shown promise as viable treatments of psychiatric disorders, including obsessive-compulsive disorder. The marble burying test is a test of compulsive-like behavior in mice, and psychedelics acting as 5-HT2AR agonists can reduce digging in this test. We assessed the 5-HT2R contribution to the mechanisms of two 5-HT2A agonists on digging behavior in female NMRI mice, using citalopram as a reference compound. While the 5-HT2AR antagonist M100907 blocked the effect of DOI and the 5-HT2CR antagonist SB242084 blocked the effect of citalopram, neither antagonist blocked the effect of psilocybin. This study confirms 5-HT2AR agonism as a mechanism for reduced compulsive-like digging in the MB test and suggests that 5-HT2A and 5-HT2CRs can work in parallel on this type of behavior. Our results with psilocybin suggest that a 5-HT2R-independent mechanism also contributes to the effect of psilocybin on repetitive digging behavior.