Dynamics of the dopaminergic system as a key component to the understanding of depression.
For decades, clinical treatment of depression has usually involved antidepressants that target noradrenergic and serotonergic neurotransmission. Over the past half century, no genuinely ground-breaking progress has been made in the pharmacological development of antidepressant drugs. Dopaminergic mesolimbic and mesocortical systems are involved in hedonia and motivation, two core symptoms of depression. However, their role in the pathophysiology of depression and their manipulation to treat depression has received little attention. Recent findings indicate the potential usefulness of monitoring limbic dopaminergic dynamics in combination with mathematical analysis. In this chapter comprehensive review of data from animal models, genetics, neuroimaging and human clinical trials that strengthen the case for dopaminergic dysfunction in the pathophysiology of major depression. This chapter focuses on recent convergence of data describing the fluctuation in activity of the mesolimbic dopaminergic system, and discusses its crucial role in manifestation of depressive-like behavior. Decoding the functionality of the dopaminergic system is important to the understanding of depression and the development of future efficient antidepressant treatments.
Yadid
Gal
G
Neuropharmacology Laboratory, The Mina and Everard Goodman Faculty of Life Sciences and the Leslie and Susan Gonda (Goldshmied) Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan 52900, Israel. yadidg@mail.biu.ac.il
Friedman
Alexander
A
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003866:Depressive Disorder / Q000188:drug therapy / Q000503:physiopathology*; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D008032:Limbic System / Q000033:anatomy & histology / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000502:physiology; D009714:Nucleus Accumbens / Q000378:metabolism / Q000503:physiopathology; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000378:metabolism / Q000503:physiopathology
D000928:Antidepressive Agents; D011985:Receptors, Serotonin; D012701:Serotonin; D004298:Dopamine