Pharmacology of 5-HT2 Modulation of Amygdala & Hypothalamus in Anxiety Disorders

Abstract

“Anxiety disorders” is a blanket term covering several different forms of abnormal and pathological fear and anxiety, and is often comorbid with other mental disorders, particularly clinical depression. These conditions are often related to stressful life experiences, especially when chronic and traumatic. Stress appears to act as a predisposing and precipitating factor in these psychiatric conditions (Strohle and Holsboer, 2003). One particular, extreme case is post traumatic stress disorder (PTSD), a chronic anxiety disorder developed in the aftermath of traumatic stress exposure and persisting long after the removal of the participating stressors. Advances in cellular and molecular biology and imaging technology have opened several lines of inquiry into the pathogenesis and pharmacotherapy of the anxiety disorders. Dysregulation of neurotransmitter systems, alteration of signal transduction pathways, and reshaping of brain circuitry are all being explored. The availability of animal models of anxiety disorders developed from the “learned helplessness” stress paradigm, in particular, has been a great aid in elucidation of disease etiology and pathophysiology, as well as in the development of more efficacious pharmacological interventions (Drevets, 2003;Maier and Watkins, 2005;Minor and Hunter, 2002). Among several hypotheses for the pathogenesis of anxiety disorders, dysregulation of the serotonergic system has received particular attention in the field since the evidence from both preclinical and animal model studies is substantial and often complementary. In this chapter, we focus on a subset of the serotonergic system, the 5-HT2 receptor system, and review both clinical and preclinical evidence regarding the involvement of this receptor in the pathophysiology of anxiety disorders.