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
Summary
Ketamine significantly enhances locomotion, particularly in adolescent C57BL/6J mice, with a notable increase in distance traveled and speed after doses of 25 mg/kg and 50 mg/kg. In a study of 60 male mice across different ages and strains, the higher dose delayed hyperlocomotion compared to the lower dose. Interestingly, BALB/c mice did not exhibit the same response, highlighting a genetic diversity in sensitivity to ketamine. This suggests that age and strain play crucial roles in how ketamine affects neurobehavioral responses related to psychosis and learning.
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.