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Pharmacological and behavioral characterization of the 5-HT2A receptor in C57BL/6N mice

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Abstract

Rationale

The serotonin (5-HT) 2A receptor is implicated in numerous psychiatric disorders, making it an important, clinically relevant target. Despite the availability of transgenic mouse lines, the native mouse 5-HT2A receptor is not well-characterized.

Objectives

The goals of the current study were to determine 5-HT2A and 5-HT2C receptor densities in mouse cortex, establish a pharmacological profile of the mouse 5-HT2A receptor, and determine the effects of chronic drug treatment on 5-HT2A receptor density and 5-HT2A receptor-mediated behavior.

Methods

Receptor densities were determined in cortex and frontal cortex via saturation binding assays using [3H]ketanserin or [3H]mesulergine. A pharmacological profile was established by displacing [3H]ketanserin binding with several ligands. Chronic treatment with 5-HT2A/2C receptor agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI), 5-HT2A receptor antagonist, MDL 11939, or vehicle was followed by 5-HT2A receptor density determination. Head twitch responses (HTRs) were counted on select days.

Results

Mice had high 5-HT2A, but low 5-HT2C receptor densities. Ligand binding affinities for mouse 5-HT2A receptors correlated with rat, but not rabbit or human, affinities. Chronically DOI-treated mice displayed reduced HTRs and 5-HT2A receptor density compared to saline-treated mice. Receptor density was unchanged following chronic treatment with MDL 11939.

Conclusions

The current study provides some basic information about mouse 5-HT2A and 5-HT2C receptors and provides comparisons to rats, rabbits, and humans. The current chronic agonist treatment study demonstrated an important similarity between the 5-HT2A receptor in mice, rats, and rabbits, while antagonist treatment revealed an interesting difference from previous studies in rabbits.

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Acknowledgments

The authors wish to thank Dr. James Barrett for reviewing this manuscript, Dr. Anthony Romano for assistance with statistical analysis, Dr. Laura Scarlota for assistance dissecting mouse cortices and frontal cortices, and the two anonymous reviewers of this article, whose comments, suggestions, and criticism helped improve this manuscript considerably.

Funding support provided by the Department of Pharmacology and Physiology, Drexel University College of Medicine.

The authors have no conflicts of interest to declare. The authors have full control of all primary data and agree to allow the journal to review the data if desired.

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  1. Drexel University College of Medicine, Philadelphia, PA, 19102, USA

    John P. Dougherty & Vincent J. Aloyo

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  1. John P. Dougherty
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Correspondence to John P. Dougherty.

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Dougherty, J.P., Aloyo, V.J. Pharmacological and behavioral characterization of the 5-HT2A receptor in C57BL/6N mice. Psychopharmacology 215, 581–593 (2011). https://doi.org/10.1007/s00213-011-2207-6

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