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Updated: May 9, 2026
07:56
A Plate-Based Assay for the Measurement of Endogenous Monoamine Release in Acute Brain Slices
Published on: August 11, 2021
Subanesthetic doses of ketamine transiently decrease serotonin transporter activity: a PET study in conscious
Shigeyuki Yamamoto1, Hiroyuki Ohba, Shingo Nishiyama
1Central Research Laboratory, Hamamatsu Photonics KK, Hamakita, Japan.
Summary
Subanesthetic ketamine rapidly reduces depression by inhibiting the serotonin transporter (SERT). This effect is dose-dependent and transient, enhancing serotonin transmission in the brain. Further research is needed to explore combined therapeutic effects.
Area of Science:
- Neuroscience
- Pharmacology
- Psychiatry
Background:
- Subanesthetic ketamine exhibits rapid antidepressant effects, but its neurobiological mechanisms are not fully understood.
- The role of serotonergic systems in ketamine's antidepressant action requires further elucidation.
Purpose of the Study:
- To investigate the effects of subanesthetic ketamine doses on serotonergic systems in conscious monkeys.
- To determine ketamine's impact on the serotonin transporter (SERT) and serotonin 1A receptor (5-HT1A-R).
Main Methods:
- Positron emission tomography (PET) with [(11)C]DASB was used to measure serotonin transporter (SERT) binding in vivo.
- Ketamine was administered intravenously at subanesthetic doses (0.5 or 1.5 mg/kg).
- Microdialysis was employed to measure extracellular serotonin levels in the prefrontal cortex.
Main Results:
- Ketamine infusion caused a dose-dependent, transient reduction in [(11)C]DASB binding to SERT.
- No significant changes were observed in serotonin 1A receptor (5-HT1A-R) or dopamine transporter (DAT) binding.
- Ketamine infusion transiently increased extracellular serotonin levels in the prefrontal cortex.
Conclusions:
- Subanesthetic ketamine selectively enhances serotonergic transmission through SERT inhibition.
- This SERT inhibition mechanism likely contributes to ketamine's rapid antidepressant effects.
- Further studies should explore the synergistic antidepressant potential of combined SERT and NMDA receptor inhibition.
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