Ketamine administration in early postnatal life as a tool for mimicking Autism Spectrum Disorders core symptoms.
M. Bove, Stefania Schiavone, Paolo Tucci, V. Sikora, S. Dimonte, A. Colia, M. Morgese, Luigia Trabace
Progress in Neuro-Psychopharmacology and Biological Psychiatry April 1, 2022 DOI: 10.1016/j.pnpbp.2022.110560 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal model study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | Ketamine |
| Duration | Ketamine administered at postnatal days 7, 9 and 11; behavioural testing in adult mice |
| Measures | Marble Burying, Hole Board, Olfactory and Social tests |
| Topics | Esketamine Ketamine |
| Key points | The authors report that mice given ketamine on postnatal days 7, 9, and 11 showed increased stereotyped behaviours, social impairments, and anxiety-like behaviour as adults, along with decreased BDNF and increased GFAP in the hippocampus and altered glutamate and GABA levels in the amygdala and hippocampus. They propose that early ketamine administration may be a suitable animal model of ASD with face validity for specific symptoms. |
Abstract
Autism Spectrum Disorders (ASD) core symptoms include deficits of social interaction, stereotyped behaviours, dysfunction in language and communication. Beyond them, several additional symptoms, such as cognitive impairment, anxiety-like states and hyperactivity are often occurring, mainly overlapping with other neuropsychiatric diseases. To untangle mechanisms underlying ASD etiology, and to identify possible pharmacological approaches, different factors, such as environmental, immunological and genetic ones, need to be considered. In this context, ASD animal models, aiming to reproduce the wide range of behavioural phenotypes of this uniquely human disorder, represent a very useful tool. Ketamine administration in early postnatal life of mice has already been studied as a suitable animal model resembling psychotic-like symptoms. Here, we investigated whether ketamine administration, at postnatal days 7, 9 and 11, might induce behavioural features able to mimic ASD typical symptoms in adult mice. To this aim, we developed a 4-days behavioural tests battery, including Marble Burying, Hole Board, Olfactory and Social tests, to assess repetitive and stereotyped behaviour, social deficits and anxiety-like symptoms. Moreover, by using this mouse model, we performed neurochemical and biomolecular analyses, quantifying neurotransmitters belonging to excitatory-inhibitory pathways, such as glutamate, glutamine and gamma-aminobutyric acid (GABA), as well as immune activation biomarkers related to ASD, such as CD11b and glial fibrillary acidic protein (GFAP), in the hippocampus and amygdala. Possible alterations in levels of brain-derived neurotrophic factor (BDNF) expression in the hippocampus and amygdala were also evaluated. Our results showed an increase in stereotyped behaviours, together with social impairments and anxiety-like behaviour in adult mice, receiving ketamine administration in early postnatal life. In addition, we found decreased BDNF and enhanced GFAP hippocampal expression levels, accompanied by elevations in glutamate amount, as well as reduction in GABA content in amygdala and hippocampus. In conclusion, early ketamine administration may represent a suitable animal model of ASD, exhibiting face validity to mimic specific ASD symptoms, such as social deficits, repetitive repertoire and anxiety-like behaviour.
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 3
- The immune regulatory mechanism of ketamine-induced psychiatric disorders: A new perspective on drug-induced psychiatric symptoms. Progress in Neuro-Psychopharmacology and Biological Psychiatry January 10, 2025
- Local activity alterations in autism spectrum disorder correlate with neurotransmitter properties and ketamine induced brain changes. medRxiv October 21, 2024
- Therapeutic potential of classic and non-classic psychedelics in neurodevelopmental disorders: Opportunities and challenges Pharmacological Research August 26, 2026