5‐HT2 receptors and anxiety

The present overview explores the role of the 5‐HT2 receptor subtypes (5‐HT2A, 5‐HT2B, and 5HT2C) 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.