Possible involvement of serotonin receptors in anxiety disorders

Abstract

An overview of the behavioral, electrophysiological and neurochemical data found in the literature concerning the involvement of serotonin (5-HT) receptors in the regulation of anxiety was presented on the basis of animal models. At present, 5-HT receptors are classified into 7 families including at least 14 subtypes. Among these 5-HT receptors, it is conceivable that 5-HT_1A-receptor-mediated effects are the most important part of the mechanism of anxiety. The demonstrated efficacy of 5-HT_1A-receptor partial agonists in anxiety disorders has emphasized the importance of these receptors. Enhanced anxiety was observed in mutant mice lacking 5-HT_1A receptors. In 5-HT_1B receptors knockout mice, on the other hand, aggressive behavior was increased. Some of the selective antagonists acting on 5-HT₂ and 5-HT₃ receptors have shown the anxiolytic effects in various animal models. Inactivation of mRNA encoding 5-HT₆ receptors using antisense oligonucleotide produced decreases in cortical 5-HT release enhanced by anxiety. These observations lead to the suggestion that different mechanisms, mediated by various 5-HT receptors, are involved in the pathogenesis of anxiety.