Multiplicity of anxiety and serotonin nervous system

Abstract

It has been recently suggested that the central serotonin (5-HT) nervous system may be involved in the modulation of anxiety. Especially, the possible importance of 5-HT_1A receptors in anxiety was raised by evidence that the anxiolytic properties of 5-HT_1A-receptor agonists have now been confirmed in clinical studies. On the other hand, in preclinical studies using various animal models of anxiety, these novel agents tend to have weak and/or variable effects in some paradigms used to detect the anxiolytic activities of benzodiazepines. These differential patterns of drug effects within various models promote the concept of “multiplicity of anxiety”. Recently, a new experimental model called the T-maze was developed in attempts to analyze a different type of anxiety; i.e., conditioned fear and unconditioned fear response. The results of a series of behavioral studies using the T-maze test suggest that distinct 5-HT pathways may modulate the different classes of anxiety. In our recent studies using the hole-board test, apparent differential behavioral effects between benzodiazepine anxiolytics and 5-HT_1A agonists on emotionality of stressed mice were also observed. These results suggest that benzodiazepine or 5-HT_1A receptors may play a different role in modulating emotionality. These studies may provide new information to investigate the pathophysiological characteristics of various types of anxiety disorders and to develop novel therapeutic agents.