5-HT2 receptors and anxiety

The present overview explores the role of the 5-HT2 receptor subtypes (5-HT2A, 5-HT2B, and 5HT(2C)) in anxiety models in animals with clinical consideration for the development of anxiolytic drugs in humans. The anxiolytic activities of the serotonin-selective reuptake inhibitor (SSRI) drug paroxetine or the serotonin-noradrenaline reuptake inhibitor (SNRI)drug venlafaxine, respectively, involve 5-HT2A receptors and both 5-HT2A and 5-HT2B receptors. The anxiolytic-like effects of [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane] (DOI) in the four-plates test and elevated plus maze test indicate a reduced serotonergic activity in the hippocampus and hypothalamus, implicating these structures in the anxiolytic-like effects subsequent to 5-HT2A receptor stimulation. The aim of this report was thus to evaluate further the possible involvement of the specific 5-HT2 receptor subtypes in anxiety-related responses by reassessing the effects of well-known 5-HT2 receptor agonists and antagonists and comparing them to new unfamiliar molecules. Of greater potential importance is the fact that most 5-HT2 receptor antagonists tested are non-selective for the 5-HT2 receptor subtypes, displaying high affinities for 5-HT2A, 5-HT2B and 5-HT2C sites. Drug Dev. Res. 65:133-140, 2005. (c) 2005 Wiley-Liss, Inc.