Dopamine System Dysregulation in Major Depressive Disorders

Belujon, Pauline; Grace, Anthony A.

doi:10.1093/ijnp/pyx056

Cited by 553 publications

(376 citation statements)

References 156 publications

(174 reference statements)

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“…Inhibition in activity at the DA receptor in the striatal region via a decrease in the concentrations of calcium and sodium channels at the presynaptic ending results in a significant decrease in locomotor activity (60). Thus, DA has been determined to play a vital role during the pathogenesis of depression (61). Along with DA, 5-HT has also been suggested as an important neurotransmitter that is involved in the pathogenesis of major depressive disorders (55).…”

Section: Discussionmentioning

confidence: 99%

Attenuation of reserpine‑induced fibromyalgia via ROS and serotonergic pathway modulation by fisetin, a plant flavonoid polyphenol

Yao

Kandhare

et al. 2019

Exp Ther Med

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Fibromyalgia (FM) is a chronic complex musculoskeletal disorder characterized by widespread musculoskeletal pain accompanied by fatigue, sleep disturbance, memory defects and mood changes. Fisetin, a plant flavonoid polyphenol, has been reported to possess potent antioxidant, antinociceptive and neuroprotective activities. The present study aimed to evaluate the efficacy of fisetin against reserpine-induced FM (RIF) in rats. RIF was induced in male Wistar rats (180-220 gm) using reserpine (1 mg/kg; subcutaneous; once daily for 3 consecutive days) and the rats were treated with fisetin (5, 10 and 25 mg/kg) for 21 days. Various behavioral, biochemical and molecular parameters were evaluated. Administration of reserpine induced allodynia, hyperalgesia and depression, which were significantly ameliorated (P<0.05) by fisetin (10 and 25 mg/kg), as reflected by an increase in paw and tail withdrawal latency, increased paw withdrawal threshold, and decreased immobility time. Reserpine led to decreased biogenic amine levels [5-hydroxytryptamine (5-HT), noradrenaline (NA) and dopamine (DA)] and increased the ratio to their metabolite 3,4-dihydroxyphenylacetic acid. 5-hydroxyindoleacetic acid in the spinal cord, thalamus and prefrontal cortex was significantly decreased (P<0.05) by fisetin. Immunohistological analysis of brain tissue revealed that fisetin significantly inhibited (P<0.05) reserpine-induced depletion of 5-HT. It also significantly inhibited (P<0.05) elevated oxido-nitrosative stress and reactive oxygen species (ROS) levels, as analyzed by flow cytometry in RIF rats. Fisetin exerts its antinociceptive and anti-depressive potential via modulation of decreased levels of biogenic amines (5-HT, NA and DA), elevated oxido-nitrosative stress and ROS to ameliorate allodynia, hyperalgesia, and depression in experimental RIF.

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Section: Discussionmentioning

confidence: 99%

Attenuation of reserpine‑induced fibromyalgia via ROS and serotonergic pathway modulation by fisetin, a plant flavonoid polyphenol

Yao

Kandhare

et al. 2019

Exp Ther Med

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“…The GABA and glutamate systems, the primary inhibitory and excitatory transmitters in the brain, have been shown to be altered in MDD (Godfrey et al, 2018;Voineskos et al, 2019). As well as this, neuromodulators such as serotonin and dopamine, which influence neural excitability, are known to be affected in MDD (Belujon and Grace, 2017;Morrissette and Stahl, 2014) and to play a role in cortical activity changes between EC and EO conditions (Wan et al, 2019). It thus seems possible that the reported changes in cortical dynamic reactivity are related to changes in these systems (Hu et al, 2019;Ramirez-Mahaluf et al, 2017;Wiebking et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Intrinsic activity temporal structure reactivity to behavioural state change is correlated with depressive symptoms

Duncan

Hsu

Cheng

et al. 2019

Preprint

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Patients with major depressive disorder (MDD) tend to focus their thoughts on their personal problems and negative self-reflection. This negative self-focus has a major impact on patient quality of life and is associated with a range of cognitive deficits. Self-related thoughts, such as those seen in rumination, have been associated with intrinsic activity within cortical midline structures. In normal conditions this intrinsic activity is responsive to behavioural state, changing as an individual switches from an internally to externally oriented context. It was hypothesised that this responsiveness would be blunted in patients with MDD (n = 26; control n = 37) and that the degree to which an individual was fixed in a particular intrinsic state would be correlated with reported ruminatory behaviours. This was tested by measuring intrinsic EEG activity temporal structure, quantified with detrended fluctuation analysis (DFA), in eyes-closed and eyes-open task-free states and contrasting between the conditions. The difference between the internally oriented eyes-closed and externally oriented eyes-open states was then correlated with ruminatory behaviour, measured with the Rumination Response Scale. Healthy controls showed a robust beta band DFA change between states, moving from a critical to sub-critical activity state with the opening of the eyes. This change was not seen in MDD patients, with the eyes-closed DFA remaining similar to that in eyes-open. A negative correlation was seen between the DFA difference and rumination scores over the midline electrodes. These results identify a reduced reactivity of intrinsic activity properties in MDD that is related to greater ruminative symptoms.

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“…26,27 In recent years, however, basic and clinical studies have demonstrated that DA is also involved in the pathogenesis of depression. 28 As is well known, the delivery process of typical neurotransmitters roughly includes the following steps: docking of synaptic vesicles on the presynaptic membrane, fusion of synaptic vesicles with the presynaptic membrane, the release of neurotransmitters and the clearance of neurotransmitters. 29 Abnormal adjustment of any one of these steps will impede the transmission of neurotransmitters.…”

Section: F I G U R Ementioning

confidence: 99%

Proteomics‐based screening of the target proteins associated with antidepressant‐like effect and mechanism of Saikosaponin A

Guo

Zhang

Gao

et al. 2019

J Cellular Molecular Medi

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Depression is a commonly occurring neuropsychiatric disease with an increasing incidence rate. Saikosaponin A (SA), a major bioactive component extracted from Radix Bupleuri, possesses anti‐malignant cell proliferation, anti‐inflammation, anti‐oxidation and liver protective effects. However, few studies have investigated SA’s antidepressant effects and pharmacological mechanisms of action. Our study aimed to explore the anti‐depression effect of SA and screen the target proteins regulated by SA in a rat model of chronic unpredictable mild stress (CUMS)‐induced depression. Results showed that 8‐week CUMS combined with separation could successfully produce depressive‐like behaviours and cause a decrease of dopamine (DA) in rat hippocampus, and 4‐week administration of SA could relieve CUMS rats’ depressive symptoms and up‐regulated DA content. There were 15 kinds of significant differentially expressed proteins that were detected not only between the control and CUMS groups, but also between the CUMS and SA treatment groups. Proline‐rich transmembrane protein 2 (PRRT2) was down‐regulated by CUMS while up‐regulated by SA. These findings reveal that SA may exert antidepressant effects by up‐regulating the expression level of PRRT2 and increasing DA content in hippocampus. The identification of these 15 differentially expressed proteins, including PRRT2, provides further insight into the treatment mechanism of SA for depression.

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Dopamine System Dysregulation in Major Depressive Disorders

Cited by 553 publications

References 156 publications

Attenuation of reserpine‑induced fibromyalgia via ROS and serotonergic pathway modulation by fisetin, a plant flavonoid polyphenol

Attenuation of reserpine‑induced fibromyalgia via ROS and serotonergic pathway modulation by fisetin, a plant flavonoid polyphenol

Intrinsic activity temporal structure reactivity to behavioural state change is correlated with depressive symptoms

Proteomics‐based screening of the target proteins associated with antidepressant‐like effect and mechanism of Saikosaponin A

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