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. 2017 Dec 1;20(12):1036-1046.
doi: 10.1093/ijnp/pyx056.

Dopamine System Dysregulation in Major Depressive Disorders

Free PMC article

Dopamine System Dysregulation in Major Depressive Disorders

Pauline Belujon et al. Int J Neuropsychopharmacol. .
Free PMC article


Anhedonia is considered a core feature of major depressive disorder, and the dopamine system plays a pivotal role in the hedonic deficits described in this disorder. Dopaminergic activity is complex and under the regulation of multiple brain structures, including the ventral subiculum of the hippocampus and the basolateral amygdala. Whereas basic and clinical studies demonstrate deficits of the dopaminergic system in depression, the origin of these deficits likely lies in dysregulation of its regulatory afferent circuits. This review explores the current information regarding the afferent modulation of the dopaminergic system and its relevance to major depressive disorder, as well as some of the system-level effects of novel antidepressants such as agomelatine and ketamine.

Keywords: amygdala; animal models; depression; dopamine; hippocampus; ketamine.


Figure 1.
Figure 1.
Afferent regulation of the dopamine (DA) system. The DA system is under regulation by an inhibitory circuit including the basolateral amygdala (BLA)-ventral pallidum (VP) pathway that is activated by the infralimbic subregion (ilPFC), as well as an activating circuit. including the Re-ventral subiculum of the hippocampus (vSub)-nucleus accumbens (NAc)-VP pathway that is inhibited by the ilPFC. The result is that at baseline, about one-half of the VTA DA neurons are firing spontaneously. Only DA neurons that fire spontaneously can fire in response to rapid, phasic activation with bursts of action potentials, due to activation of pedunculopontine tegmental nucleus (PPTg) afferents.
Figure 2.
Figure 2.
Afferent dysregulation of the dopamine (DA) system in major depressive disorder (MDD). In animal models of depression, the DA system is downregulated, as measured by a decrease in the number of DA neurons that fire spontaneously. This decrease is due to hyperactivity of the infralimbic subregion (ilPFC), driving activity in the inhibitory basolateral amygdala (BLA)-ventral pallidum (VP) pathway while attenuating excitation via the Re-ventral subiculum of the hippocampus (vSub)-nucleus accumbens (NAc)-VP pathway.

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