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.
Keywords:
5-HT(2A); 5-HT(2C); Compulsivity; Marble burying; Psilocybin; Serotonin.
Copyright © 2020 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aminopyridines / pharmacology
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Amphetamines / pharmacology
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Animals
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Behavior, Animal / drug effects
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Citalopram / pharmacology
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Compulsive Behavior / drug therapy*
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Disease Models, Animal
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Female
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Fluorobenzenes / pharmacology
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Indoles / pharmacology
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Mice
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Piperidines / pharmacology
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Psilocybin / administration & dosage
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Psilocybin / pharmacology*
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Receptor, Serotonin, 5-HT2A / drug effects*
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Receptor, Serotonin, 5-HT2C / drug effects*
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Selective Serotonin Reuptake Inhibitors / pharmacology
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Serotonin 5-HT2 Receptor Agonists / administration & dosage
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Serotonin 5-HT2 Receptor Agonists / pharmacology*
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Serotonin Antagonists / administration & dosage
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Serotonin Antagonists / pharmacology*
Substances
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5-hydroxytryptamine2C receptor, mouse
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6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline
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Aminopyridines
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Amphetamines
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Fluorobenzenes
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Htr2a protein, mouse
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Indoles
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Piperidines
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Receptor, Serotonin, 5-HT2A
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Receptor, Serotonin, 5-HT2C
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Serotonin 5-HT2 Receptor Agonists
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Serotonin Antagonists
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Serotonin Uptake Inhibitors
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Citalopram
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Psilocybin
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volinanserin
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4-iodo-2,5-dimethoxyphenylisopropylamine