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 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Female NMRI mice |
| Interventions | DOI psilocybin citalopram M100907 SB242084 |
| Topics | Psilocybin Serotonin |
| Keywords | Citalopram Hallucinogen Pharmacology Receptor antagonist Ketanserin Digging |
| Citations | 60 |
| Key findings | 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.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 50
- Psilocybin facilitates fear extinction in mice by promoting hippocampal neuroplasticity. Chinese medical journal December 20, 2023
- Psychedelic Therapy's Transdiagnostic Effects: A Research Domain Criteria (RDoC) Perspective Frontiers in Psychiatry December 17, 2021
- Effect of psilocybin on marble burying in ICR mice: role of 5-HT1A receptors and implications for the treatment of obsessive-compulsive disorder. Translational Psychiatry May 10, 2023
- Mechanisms and molecular targets surrounding the potential therapeutic effects of psychedelics. Molecular Psychiatry September 1, 2023
- Potential Differences in Psychedelic Actions Based on Biological Sex. Endocrinology July 1, 2024
and 45 more in the library
Cites 8
- Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder The Journal of Clinical Psychiatry November 15, 2006
- Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. European Neuropsychopharmacology May 20, 2016
- Psychedelics as Medicines: An Emerging New Paradigm Clinical Pharmacology & Therapeutics November 4, 2016
- Effects ofPsilocybe argentipeson Marble-Burying Behavior in Mice Bioscience Biotechnology and Biochemistry August 23, 2009
- The selective 5-HT2A receptor agonist 25CN-NBOH: structure-activity relationship, in vivo pharmacology, and in vitro and ex vivo binding characteristics of [3H]25CN-NBOH. Biochemical Pharmacology April 13, 2020
and 3 more in the library