Ketamine-Induced Loss of Phenotype of Fast-Spiking Interneurons Is Mediated by NADPH-Oxidase
M. Margarita Behrens, Sameh S. Ali, Diep N. Dao, Jacinta Lucero, Grigoriy Shekhtman, Kevin L. Quick, Laura L. Dugan
Science December 6, 2007 DOI: 10.1126/science.1148045 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | Ketamine |
| Topics | Ketamine Esketamine |
| Keywords | Nadph oxidase Parvalbumin Inhibitory postsynaptic potential Superoxide Nmda receptor Gabaa receptor Glutamate receptor Oxidase test Pharmacology Biochemistry Enzyme |
| Citations | 590 |
| Key findings | Ketamine-induced superoxide production via NADPH oxidase in neurons causes dysfunction of cortical fast-spiking inhibitory interneurons, which can be prevented by reducing superoxide. |
Abstract
Abuse of the dissociative anesthetic ketamine can lead to a syndrome indistinguishable from schizophrenia. In animals, repetitive exposure to this N-methyl-d-aspartate-receptor antagonist induces the dysfunction of a subset of cortical fast-spiking inhibitory interneurons, with loss of expression of parvalbumin and the gamma-aminobutyric acid-producing enzyme GAD67. We show here that exposure of mice to ketamine induced a persistent increase in brain superoxide due to activation in neurons of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Decreasing superoxide production prevented the effects of ketamine on inhibitory interneurons in the prefrontal cortex. These results suggest that NADPH oxidase may represent a novel target for the treatment of ketamine-induced psychosis.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 47
- A neurotrophic hypothesis of depression: role of synaptogenesis in the actions of NMDA receptor antagonists Philosophical transactions of the Royal Society of London. Series B, Biological sciences July 23, 2012
- Reviewing the ketamine model for schizophrenia Journal of Psychopharmacology November 20, 2013
- Ketamine: NMDA Receptors and Beyond Journal of Neuroscience November 2, 2016
- Pathophysiology of depression and innovative treatments: remodeling glutamatergic synaptic connections Dialogues in Clinical Neuroscience March 31, 2014
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
and 42 more in the library
Cites 4
- Repeated phencyclidine in monkeys results in loss of parvalbumin-containing axo-axonic projections in the prefrontal cortex. Psychopharmacology June 2007
- Phencyclidine animal models of schizophrenia: approaches from abnormality of glutamatergic neurotransmission and neurodevelopment. Neurochemistry International 2007
- A pharmacological model for psychosis based on N-methyl-D-aspartate receptor hypofunction: molecular, cellular, functional and behavioral abnormalities. Biological Psychiatry April 15, 2006
- Spatial memory deficits induced by perinatal treatment of rats with PCP and reversal effect of D-serine. Neuropsychopharmacology June 1, 2004