Pharmacological and behavioral characterization of the 5-HT2A receptor in C57BL/6N mice.
John P Dougherty, Vincent J. Aloyo
Psychopharmacology June 2011 DOI: 10.1007/s00213-011-2207-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | DOI MDL 11939 |
| Duration | Chronic treatment |
| Measures | head twitch responses, receptor density |
| Topics | Serotonin |
| Key findings | Mice had high 5-HT(2A) but low 5-HT(2C) receptor densities. Chronic DOI treatment reduced head twitch responses and 5-HT(2A) receptor density, whereas chronic MDL 11939 treatment did not alter receptor density. |
Abstract
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. 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. 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. 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. 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.