Delayed emergence of behavioral and electrophysiological effects following juvenile ketamine exposure in mice
L.R. Nagy, Robert E. Featherstone, Chang-Gyu Hahn, Steven J. Siegel
Translational Psychiatry September 15, 2015 DOI: 10.1038/tp.2015.111 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled experimental animal study Peer reviewed |
|---|---|
| Population | Juvenile mice (4 weeks of age) exposed to ketamine or control conditions |
| Intervention | Ketamine |
| Dose | 20 mg kg(-1), i.p. daily |
| Duration | 14 days of exposure; tested at 7 weeks and 12 weeks of age |
| Measures | electroencephalography (EEG) in response to auditory stimulation, event-related potential (ERP) amplitudes, social choice test, 6-arm radial water maze task |
| Topics | Esketamine Ketamine |
| Citations | 24 |
| Key findings | Juvenile ketamine exposure in mice was associated with long-lasting electrophysiological abnormalities in adulthood, including altered induced theta power and P80 ERP, and with atypical developmental trajectories in social behavior and spatial working memory. The authors argue these data support the hypothesis that adolescent ketamine exposure produces persistent changes in brain function characterized by a failure to progress along normal developmental trajectories. |
Abstract
Frequent ketamine abuse in adulthood correlates with increased risk of psychosis, as well as cognitive deficits, including disruption of higher-order executive function and memory formation. Although the primary abusers of ketamine are adolescents and young adults, few studies have evaluated its effects on juvenile cognition. Therefore, the current study analyzes the effect of adolescent ketamine exposure on cognitive development. Juvenile mice (4 weeks of age) were exposed to chronic ketamine (20 mg kg(-1), i.p. daily) for 14 days. Mice were tested immediately after exposure in the juvenile period (7 weeks of age) and again as adults (12 weeks of age). Measures included electroencephalography (EEG) in response to auditory stimulation, the social choice test, and a 6-arm radial water maze task. Outcome measures include low-frequency EEG responses, event-related potential (ERP) amplitudes, indices of social behavior and indices of spatial working memory. Juvenile exposure to ketamine was associated with electrophysiological abnormalities in adulthood, particularly in induced theta power and the P80 ERP. The social choice test revealed that ketamine-exposed mice failed to exhibit the same age-related decrease in social interaction time as controls. Ketamine-exposed mice outperformed control mice as juveniles on the radial water maze task, but did not show the same age-related improvement as adult controls. These data support the hypothesis that juvenile exposure to ketamine produces long-lasting changes in brain function that are characterized by a failure to progress along normal developmental trajectories.
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 2
Cites 8
- EFFECTS OF KETAMINE ON EXPLICIT AND IMPLICIT SUICIDAL COGNITION: A RANDOMIZED CONTROLLED TRIAL IN TREATMENT-RESISTANT DEPRESSION Depression and Anxiety March 25, 2014
- Reviewing the ketamine model for schizophrenia Journal of Psychopharmacology November 20, 2013
- Prevention and reversal of ketamine-induced schizophrenia related behavior by minocycline in mice: Possible involvement of antioxidant and nitrergic pathways Journal of Psychopharmacology September 17, 2013
- Subchronic ketamine treatment leads to permanent changes in EEG, cognition and the astrocytic glutamate transporter EAAT2 in mice Neurobiology of Disease March 22, 2021
- Preliminary analysis of positive and negative syndrome scale in ketamine-associated psychosis in comparison with schizophrenia Journal of Psychiatric Research December 24, 2014
and 3 more in the library