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  • Title: Pharmacological and behavioral characterization of the 5-HT2A receptor in C57BL/6N mice.
    Author: Dougherty JP, Aloyo VJ.
    Journal: Psychopharmacology (Berl); 2011 Jun; 215(3):581-93. PubMed ID: 21340474.
    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-HT(2A) receptor is not well-characterized. OBJECTIVES: The goals of the current study were to determine 5-HT(2A) and 5-HT(2C) receptor densities in mouse cortex, establish a pharmacological profile of the mouse 5-HT(2A) receptor, and determine the effects of chronic drug treatment on 5-HT(2A) receptor density and 5-HT(2A) receptor-mediated behavior. METHODS: Receptor densities were determined in cortex and frontal cortex via saturation binding assays using [(3)H]ketanserin or [(3)H]mesulergine. A pharmacological profile was established by displacing [(3)H]ketanserin binding with several ligands. Chronic treatment with 5-HT(2A/2C) receptor agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI), 5-HT(2A) receptor antagonist, MDL 11939, or vehicle was followed by 5-HT(2A) receptor density determination. Head twitch responses (HTRs) were counted on select days. RESULTS: Mice had high 5-HT(2A), but low 5-HT(2C) receptor densities. Ligand binding affinities for mouse 5-HT(2A) receptors correlated with rat, but not rabbit or human, affinities. Chronically DOI-treated mice displayed reduced HTRs and 5-HT(2A) 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-HT(2A) and 5-HT(2C) receptors and provides comparisons to rats, rabbits, and humans. The current chronic agonist treatment study demonstrated an important similarity between the 5-HT(2A) receptor in mice, rats, and rabbits, while antagonist treatment revealed an interesting difference from previous studies in rabbits.
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