Serotonin is a common thread linking different classes of antidepressants

Witt, Colby E.; Mena, Sergio; Holmes, Jordan; Hersey, Melinda; Buchanan, Anna Marie; Parke, Brenna; Saylor, Rachel; Honan, Lauren E.; Berger, Shane N.; Lumbreras, Sara; Nijhout, Frederik H.; Reed, Michael C.; Best, Janet; Fadel, James; Schloss, Patrick; Lau, Thorsten; Hashemi, Parastoo

doi:10.1016/j.chembiol.2023.10.009

Cited by 8 publications

(2 citation statements)

References 96 publications

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“…S6A). After systemic ketamine injection, consistent with previous reports (69)(70)(71), there was a marked increase in the 5-HT signal in control mice (fig. S6, B to D).…”

Section: Local Knockout Of Nr1 In Lhb Reduces Systemic Ketamine-induc...supporting

confidence: 92%

Brain region–specific action of ketamine as a rapid antidepressant

Chen,

Ma,

Liu

et al. 2024

Science

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Ketamine has been found to have rapid and potent antidepressant activity. However, despite the ubiquitous brain expression of its molecular target, the N -methyl- d -aspartate receptor (NMDAR), it was not clear whether there is a selective, primary site for ketamine’s antidepressant action. We found that ketamine injection in depressive-like mice specifically blocks NMDARs in lateral habenular (LHb) neurons, but not in hippocampal pyramidal neurons. This regional specificity depended on the use-dependent nature of ketamine as a channel blocker, local neural activity, and the extrasynaptic reservoir pool size of NMDARs. Activating hippocampal or inactivating LHb neurons swapped their ketamine sensitivity. Conditional knockout of NMDARs in the LHb occluded ketamine’s antidepressant effects and blocked the systemic ketamine–induced elevation of serotonin and brain-derived neurotrophic factor in the hippocampus. This distinction of the primary versus secondary brain target(s) of ketamine should help with the design of more precise and efficient antidepressant treatments.

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“…S6A). After systemic ketamine injection, consistent with previous reports (69)(70)(71), there was a marked increase in the 5-HT signal in control mice (fig. S6, B to D).…”

Section: Local Knockout Of Nr1 In Lhb Reduces Systemic Ketamine-induc...supporting

confidence: 92%

Brain region–specific action of ketamine as a rapid antidepressant

Chen,

Ma,

Liu

et al. 2024

Science

View full text Add to dashboard Cite

show abstract

“…However, compared to previous data from the Hashemi lab [ 79 ], serotonin concentrations tend to decrease with chronic stress and increase pro-inflammatory immune cells with histamine. In addition to these works, new research has also explored how ketamine changes cytokines [ 101 – 103 ], and that cytokine regulation may play a role in TRD [ 101 , 102 ]. Thus, future research could measure glutamate and cytokine changes with biosensors to understand how they change with stress, behavior, and ketamine or other antidepressants.…”

Section: Three Neurotransmitter Hypotheses Of Depression: Recent Disc...mentioning

confidence: 99%

Electrochemical and biosensor techniques to monitor neurotransmitter changes with depression

Dunham,

Venton

2024

Anal Bioanal Chem

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Depression is a common mental illness. However, its current treatments, like selective serotonin reuptake inhibitors (SSRIs) and micro-dosing ketamine, are extremely variable between patients and not well understood. Three neurotransmitters: serotonin, histamine, and glutamate, have been proposed to be key mediators of depression. This review focuses on analytical methods to quantify these neurotransmitters to better understand neurological mechanisms of depression and how they are altered during treatment. To quantitatively measure serotonin and histamine, electrochemical techniques such as chronoamperometry and fast-scan cyclic voltammetry (FSCV) have been improved to study how specific molecular targets, like transporters and receptors, change with antidepressants and inflammation. Specifically, these studies show that different SSRIs have unique effects on serotonin reuptake and release. Histamine is normally elevated during stress, and a new inflammation hypothesis of depression links histamine and cytokine release. Electrochemical measurements revealed that stress increases histamine, decreases serotonin, and leads to changes in cytokines, like interleukin-6. Biosensors can also measure non-electroactive neurotransmitters, including glutamate and cytokines. In particular, new genetic sensors have shown how glutamate changes with chronic stress, as well as with ketamine treatment. These techniques have been used to characterize how ketamine changes glutamate and serotonin, and to understand how it is different from SSRIs. This review briefly outlines how these electrochemical techniques work, but primarily highlights how they have been used to understand the mechanisms of depression. Future studies should explore multiplexing techniques and personalized medicine using biomarkers in order to investigate multi-analyte changes to antidepressants. Graphical abstract

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Antidepressants can help to prevent and manage long COVID depression, anxiety, brain fog and fatigue

Bonnet,

Kuhn

2024

Eur Arch Psychiatry Clin Neurosci

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Serotonin is a common thread linking different classes of antidepressants

Cited by 8 publications

References 96 publications

Brain region–specific action of ketamine as a rapid antidepressant

Brain region–specific action of ketamine as a rapid antidepressant

Electrochemical and biosensor techniques to monitor neurotransmitter changes with depression

Antidepressants can help to prevent and manage long COVID depression, anxiety, brain fog and fatigue

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