Prenatal exposure to ketamine in rats: Implications on animal models of schizophrenia.
Carlos Coronel-Oliveros, Renny Pacheco-Calderón
Developmental Psychobiology January 2018 DOI: 10.1002/dev.21586 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal model study Peer reviewed |
|---|---|
| Population | Pregnant Sprague-Dawley rats and their offspring |
| Intervention | Ketamine |
| Dose | 60 mg.kg-1 h-1 intramuscularly |
| Duration | Ketamine administered on gestational day 14; offspring assessed at 4 weeks and 10 weeks of age |
| Topics | Ketamine Esketamine |
| Keywords | Nmda Hippocampus Prenatal Schizophrenia |
| Key points | Prenatal ketamine exposure in rats produced hyperactivity and disinhibition in puberty and, in adulthood, cognitive impairments, social withdrawal, anxiety, depression-like and aggressive-like behaviors, plus reduced CA3 hippocampal layer thickness without changes in cell density. The authors argue these results suggest a robust link between prenatal NMDA receptor manipulation and schizophrenia. |
Abstract
Schizophrenia is a complex neuropsychiatric disorder characterized by hallucinations, delusions, anhedonia, flat affect and cognitive impairments. The aim of this study was to propose a prenatal treatment with ketamine, a psychedelic drug that acts as a non-competitive inhibitor of glutamate NMDA receptors, as a neurodevelopmental animal model of schizophrenia. The drug was applied (i.m. 60 mg.kg-1 h-1 ) in pregnant Sprague-Dawley rats on gestational Day 14. Offspring behavior was studied on pubertal (4 weeks old) and adult (10 weeks old) stages. Also, hippocampal CA1-CA3 morphology was assessed in adult animals through a Nissl stain. Results showed a disinhibition and hyperactive behavior in pubertal animals exposed to ketamine, followed in adulthood with cognitive impairments, social withdrawal, anxiety, depression, and aggressive-like behaviors. In the hippocampus, a reduction of the CA3 layer thickness was observed, without changes in cell density. These results strongly suggest a robust link between prenatal pharmacologic manipulation of NMDA receptors and schizophrenia.
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 4
- Is the antidepressant effect of ketamine separate from its psychotomimetic effect? A review of rodent models. Neuropharmacology November 1, 2024
- Structural Neurotoxic and Neuroprotective Effects of Ketamine and Esketamine in Preclinical and Human Studies: A Systematic Review Research Square May 27, 2026
- Resveratrol plays Neuroprotective role on ketamine-induced schizophrenia-like behaviors and oxidative damage in mice. Neuroscience Letters August 14, 2023
- Neuroprotective effects of curcumin-loaded nanophytosome on ketamine-induced schizophrenia-like behaviors and oxidative damage in male mice. Neuroscience Letters September 15, 2021