Potential link between antidepressant-like effects of ketamine and promotion of adult neurogenesis in the ventral hippocampus of mice.
Jun Yamada, Shozo Jinno
Neuropharmacology November 1, 2019 DOI: 10.1016/j.neuropharm.2019.107710 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study Peer reviewed |
|---|---|
| Population | Adult mice |
| Intervention | Ketamine |
| Dose | single ketamine administration |
| Topics | Esketamine Ketamine Neuroplasticity |
| Key findings | A single ketamine administration selectively promotes adult neurogenesis in the ventral hippocampus and induces greater expression of GluN2B, p-mTOR, GluA1, and BDNF in that region, correlating with antidepressant-like effects. |
Abstract
Recent studies have shown that ketamine, an open channel blocker of the N-methyl-d-aspartate receptor (NMDAR), is effective for patients with treatment-resistant depression. In this study, we aimed to elucidate the potential link between antidepressant-like effects of a single ketamine administration and dorsoventral differentiation in adult hippocampal neurogenesis. Immunohistochemical analyses revealed that elevation in the densities of neuronal progenitors and newborn granule cells by ketamine was seen in the ventral (related to emotion), but not dorsal (related to spatial memory), hippocampus in adult mice, although the densities of neural stem cells were not affected by ketamine in both the dorsal and ventral regions. Promotion of maturation of newborn granule cells by ketamine was evident in the ventral, but not dorsal, hippocampus. Behavioral analyses showed that ketamine did not affect spatial memory but ameliorated depression-related behavior. Western blot analyses showed that the basal expression of the GluN2B, but not GluN1, subunit of the NMDAR was higher in the ventral hippocampus than in the dorsal hippocampus. The induction of expression of GluN2B subunit of the NMDAR, phosphorylated mammalian target of rapamycin (p-mTOR), GluA1 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), and brain derived neurotrophic factor (BDNF), by ketamine was greater in the ventral hippocampus than in the dorsal hippocampus. Our results demonstrate that a single ketamine administration promotes adult neurogenesis in the ventral hippocampus quite selectively. Furthermore, ventral-dominant induction of the GluN2B subunit of NMDAR, p-mTOR, GluA1 subunit of AMPAR, and BDNF, in the hippocampus may underlie the unique antidepressant-like effects of ketamine.
Comparable studies
Other preclinical and animal studies on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Mice | 2023 | Experimental study | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study | |
| The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro Progenitor cells from subventricular and subgranular zones of adult mice brains | 2017 | In vitro experimental study | |
| N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo Mice | 2020 | In vitro and in vivo experimental study |
Citations in the library
Cited by 20
- Neurotrophic mechanisms underlying the rapid and sustained antidepressant actions of ketamine. Pharmacology, Biochemistry, and Behavior December 9, 2019
- Ketamine and the Future of Rapid-Acting Antidepressants Annual Review of Clinical Psychology February 9, 2021
- Ketamine: Neuroprotective or Neurotoxic? Frontiers in Neuroscience September 10, 2021
- Ketamine and its metabolites: Potential as novel treatments for depression. Neuropharmacology October 1, 2022
- Ketamine as a Treatment for Anorexia Nervosa: A Narrative Review Nutrients November 20, 2021
and 15 more in the library
Cites 14
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Ketamine: a paradigm shift for depression research and treatment Neuron March 1, 2019
- BDNF Release Is Required for the Behavioral Actions of Ketamine The International Journal of Neuropsychopharmacology October 31, 2014
- The use of ketamine as an antidepressant: a systematic review and meta‐analysis Human Psychopharmacology: Clinical and Experimental April 7, 2015
and 9 more in the library