Dynamics of the dopaminergic system as a key component to the understanding of depression
Papakostas GI.
Yadid G, Friedman A.
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.
Prog Brain Res. 2008;172:265-86.


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.
The pleasure seekers
The nucleus accumbens
The ventral pallidum and pleasure
Dopamine and dopaminergic antidepressants
Pain, motivation, pleasure and the rostral shell
Depression, dopamine and dextroamphetamine
Mesolimbic medium spiny neurons and pleasure
The magic millimeter? Locating the hedonic hotspot
Hedonic zonal shifts in the medial shell of the nucleus accumbens

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