Astroglial serotonin receptors as the central target of classic antidepressants

Major depressive disorder (MDD) presents multiple clinical phenotypes and has complex underlying pathological mechanisms. Existing theories cannot completely explain the pathophysiological mechanism(s) of MDD, while the pharmacology of current antidepressants is far from being fully understood. Astrocytes, the homeostatic and defensive cells of the central nervous system, contribute to shaping behaviors, and regulating mood and emotions. A detailed introduction on the role of astrocytes in depressive disorders is thus required, to which this chapter is dedicated. We also focus on the interactions between classic antidepressants and serotonin receptors, overview the role of astrocytes in the pharmacological mechanisms of various antidepressants, and present astrocytes as targets for the treatment of bipolar disorder. We provide a foundation of knowledge on the role of astrocytes in depressive disorders and astroglial 5-HT2B receptors as targets for selective serotonin reuptake inhibitors in vivo and in vitro.