Basic pharmacology of generalized anxiety disorder

Generalized anxiety disorder (GAD) is a chronic, disabling condition in which treatment response is often unsatisfactory. Aetiology and underlying mechanisms of GAD, as for most psychiatric disorders, remain relatively poorly understood. Preclinical research has expanded substantially in the past decade and contributed to the identification of a growing range of pharmacological targets for reducing the burden of GAD. In this chapter we describe some of the more widely used approaches for understanding the neurobiology of anxiety disorders as well as evaluating anxiolytic activity of known and potential therapeutic agents. In addition, we will focus on neurotransmitter systems implicated in generating and sustaining anxiety including the GABA, serotonin, glutamate, endocannabinoids, and neuropeptide systems. The major challenge in effective anxiolytic drug discovery is the selective targeting of receptor sub-types in anxietyrelated brain circuits