Back to Search
Start Over
Brain region-specific action of ketamine as a rapid antidepressant.
- Source :
-
Science (New York, N.Y.) [Science] 2024 Aug 09; Vol. 385 (6709), pp. eado7010. Date of Electronic Publication: 2024 Aug 09. - Publication Year :
- 2024
-
Abstract
- 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.
- Subjects :
- Animals
Male
Mice
Brain-Derived Neurotrophic Factor metabolism
Brain-Derived Neurotrophic Factor genetics
Hippocampus drug effects
Hippocampus metabolism
Mice, Inbred C57BL
Mice, Knockout
Pyramidal Cells drug effects
Pyramidal Cells metabolism
Serotonin metabolism
Antidepressive Agents pharmacology
Depression drug therapy
Depression metabolism
Habenula drug effects
Habenula metabolism
Ketamine pharmacology
Ketamine administration & dosage
Receptors, N-Methyl-D-Aspartate antagonists & inhibitors
Receptors, N-Methyl-D-Aspartate genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9203
- Volume :
- 385
- Issue :
- 6709
- Database :
- MEDLINE
- Journal :
- Science (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 39116252
- Full Text :
- https://doi.org/10.1126/science.ado7010