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.