Age, Dose, and Locomotion: Decoding Vulnerability to Ketamine in C57BL/6J and BALB/c Mice.

Ketamine, a drug abused for its psychedelic effects, alters movement differently depending on a mouse's age, strain, and dose. Adolescent and adult male mice from two strains, C57BL/6J and BALB/c, were given ketamine at 0, 25, or 50 mg/kg after a 30-minute baseline. In C57BL/6J mice, both age groups showed significantly increased distance traveled and speed after ketamine, but BALB/c mice did not. The higher dose delayed the onset of hyperlocomotion compared to the lower dose. Adolescent C57BL/6J mice showed greater locomotor activation than adults, a difference not seen in BALB/c mice. These results indicate that sensitivity to ketamine's effects on movement is biologically determined.

Study at a glance

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.