Ketamine administration during adolescence impairs synaptic integration and inhibitory synaptic transmission in the adult dentate gyrus.
Odra Santander, Sebastián B Arredondo, Francisca García-Rojas, Sebastián F Estay, Juan E Belforte, Andrés E Chávez, Lorena Varela-Nallar, Marco Fuenzalida
Progress in Neurobiology March 1, 2025 DOI: 10.1016/j.pneurobio.2025.102718 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Adult mice |
| Intervention | Ketamine |
| Topics | Ketamine Esketamine |
| Keywords | Adolescence Dentate gyrus Inhibitory synaptic transmission Parvalbumin interneurons Synaptic integration Drug effects Brain development Adolescent health Memory research |
| Citations | 3 |
| Key findings | Chronic adolescent ketamine administration expands the temporal window for synaptic integration in the inner molecular layer of the dorsal dentate gyrus and reduces inhibitory efficacy via decreased parvalbumin-positive interneuron number and function. |
Abstract
Ketamine administration during adolescence affects cognitive performance; however, its long-term impact on synaptic function and neuronal integration in the hippocampus a brain region critical for cognition remains unclear. Using functional and molecular analyses, we found that chronic ketamine administration during adolescence exerts long-term effects on synaptic integration, expanding the temporal window in an input-specific manner affecting the inner molecular layer but not the medial perforant path inputs in the adult mouse dorsal hippocampal dentate gyrus. Ketamine also alters the excitatory/inhibitory balance by reducing the efficacy of inhibitory inputs likely due to a reduction in parvalbumin-positive interneurons number and function. These findings indicate that during adolescence, ketamine exerts a strong effect on inhibitory synaptic function mediated by parvalbumin-positive neurons that ultimately impact synaptic integration in the dorsal adult dentate gyrus, which could help to understand the neurobiological and functional bases that confer greater vulnerability to the adolescent brain.
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
Cites 6
- Ketamine-Induced Loss of Phenotype of Fast-Spiking Interneurons Is Mediated by NADPH-Oxidase Science December 6, 2007
- Taming the Ketamine Tiger Anesthesiology August 6, 2010
- Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics Annual Review of Medicine October 23, 2014
- Reviewing the ketamine model for schizophrenia Journal of Psychopharmacology November 20, 2013
- Ketamine—50 years in use: from anesthesia to rapid antidepressant effects and neurobiological mechanisms Pharmacological Reports February 20, 2021
and 1 more in the library