Pharmacological and behavioral characterization of the 5-HT^sub 2A^ receptor in C57BL/6N mice

• Published in: Psychopharmacology Vol. 215; no. 3; p. 581
• Main Authors: Dougherty, John P, Aloyo, Vincent J
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer Nature B.V 01.06.2011
• Subjects: Animal behavior; Neurology; Neurotransmitters; Psychopharmacology; Rodents
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-011-2207-6

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^sub 2A^ receptor is not well-characterized. The goals of the current study were to determine 5-HT^sub 2A^ and 5-HT^sub 2C^ receptor densities in mouse cortex, establish a pharmacological profile of the mouse 5-HT^sub 2A^ receptor, and determine the effects of chronic drug treatment on 5-HT^sub 2A^ receptor density and 5-HT^sub 2A^ receptor-mediated behavior. Receptor densities were determined in cortex and frontal cortex via saturation binding assays using [^sup 3^H]ketanserin or [^sup 3^H]mesulergine. A pharmacological profile was established by displacing [^sup 3^H]ketanserin binding with several ligands. Chronic treatment with 5-HT^sub 2A/2C^ receptor agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI), 5-HT^sub 2A^ receptor antagonist, MDL 11939, or vehicle was followed by 5-HT^sub 2A^ receptor density determination. Head twitch responses (HTRs) were counted on select days. Mice had high 5-HT^sub 2A^, but low 5-HT^sub 2C^ receptor densities. Ligand binding affinities for mouse 5-HT^sub 2A^ receptors correlated with rat, but not rabbit or human, affinities. Chronically DOI-treated mice displayed reduced HTRs and 5-HT^sub 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^sub 2A^ and 5-HT^sub 2C^ receptors and provides comparisons to rats, rabbits, and humans. The current chronic agonist treatment study demonstrated an important similarity between the 5-HT^sub 2A^ receptor in mice, rats, and rabbits, while antagonist treatment revealed an interesting difference from previous studies in rabbits.[PUBLICATION ABSTRACT]