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Investigating the role of 5-HT2A and 5-HT2C receptor activation in the effects of psilocybin, DOI, and citalopram on marble burying in mice

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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.

Odland, A. U., Kristensen, J. L., & Andreasen, J. T. (2021). Investigating the role of 5-HT2A and 5-HT2C receptor activation in the effects of psilocybin, DOI, and citalopram on marble burying in mice. Behavioural brain research, 401, 113093. https://doi.org/10.1016/j.bbr.2020.113093

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