Age, Dose, and Locomotion: Decoding Vulnerability to Ketamine in C57BL/6J and BALB/c Mice.
Wen-Chien Chen, Tzong-Shi Wang, Fang-Yu Chang, Po-An Chen, Yi-Chyan Chen
Biomedicines June 25, 2023 DOI: 10.3390/biomedicines11071821 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Male C57BL/6J and BALB/c mice in adolescence and adulthood |
| Intervention | Ketamine |
| Dose | 0, 25, and 50 mg/kg |
| Duration | 60 minutes post-injection after a 30-minute baseline habituation |
| Topics | Ketamine Esketamine |
| Keywords | Nmda Age Dose effect Genetic diversity Learning Locomotion Pharmacological response Psychosis Strain |
| Citations | 12 |
| Key findings | Ketamine-induced hyperlocomotion was dose- and age-dependent in C57BL/6J mice but absent in BALB/c mice, indicating biological determination of sensitivity. |
Abstract
Ketamine has been abused as a psychedelic agent and causes diverse neurobehavioral changes. Adolescence is a critical developmental stage but vulnerable to substances and environmental stimuli. Growing evidence shows that ketamine affects glutamatergic neurotransmission, which is important for memory storage, addiction, and psychosis. To explore diverse biological responses, this study was designed to assess ketamine sensitivity in mice of different ages and strains. Male C57BL/6J and BALB/c mice were studied in adolescence and adulthood separately. An open field test assessed motor behavioral changes. After a 30-min baseline habituation, mice were injected with ketamine (0, 25, and 50 mg/kg), and their locomotion was measured for 60 min. Following ketamine injection, the travelled distance and speed significantly increased in C57BL/6J mice between both age groups (p < 0.01), but not in BALB/c mice. The pattern of hyperlocomotion showed that mice were delayed at the higher dose (50 mg/kg) compared to the lower dose (25 mg/kg) of ketamine treatment. Ketamine accentuated locomotor activation in adolescent C57BL/6J mice compared to adults, but not in the BALB/c strain. Here, we show that ketamine-induced locomotor behavior is modulated by dose and age. The discrepancy of neurobehaviors in the two strains of mice indicates that sensitivity to ketamine is biologically determined. This study suggests that individual vulnerability to ketamine's pharmacological responses varies biologically.
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
- Ketamine evokes acute behavioral effects via μ-opioid receptor expressing neurons of the central amygdala. Biological Psychiatry May 5, 2025
- Opioid receptor expressing neurons of the central amygdala gate behavioral effects of ketamine in mice. bioRxiv : the preprint server for biology March 6, 2024
- Chlorogenic Acid Attenuates Schizophrenia-Like Behavioral Deficits and Neuroinflammation in a Ketamine-Induced Mouse Model
Cites 21
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Esketamine Nasal Spray for Rapid Reduction of Depressive Symptoms in Patients With Major Depressive Disorder Who Have Active Suicide Ideation With Intent: Results of a Phase 3, Double-Blind, Randomized Study (ASPIRE II) The International Journal of Neuropsychopharmacology August 26, 2020
- Pharmacological and behavioral divergence of ketamine enantiomers: implications for abuse liability Molecular Psychiatry April 15, 2021
- The effects of ketamine on dopaminergic function: meta-analysis and review of the implications for neuropsychiatric disorders Molecular Psychiatry October 3, 2017
and 16 more in the library