Biological variations in ketamine sensitivity: insights from hyperlocomotion to psychotomimetic features in genetically diverse mouse strains.
Psychiatry research April 1, 2026 Wen-Huei Siao, Tzong-Shi Wang, Liang-Chun Wang et al.
Ketamine, a drug that blocks NMDA receptors and produces schizophrenia-like effects, causes different behavioral responses depending on the mouse strain and dose. Adolescent mice from four strains—C57BL/6J, DBA, BALB/c, and 129S1—received ketamine injections of 0, 25, or 50 mg/kg, and their movement in an open field was tracked. Before and after treatment, locomotor activity varied significantly among strains, with C57BL/6J mice most active and 129S1 mice least active. Ketamine dose-dependently increased movement in C57BL/6J mice, caused brief excitation in DBA mice at 25 mg/kg, delayed excitation in BALB/c mice at 50 mg/kg, and minimal changes in 129S1 mice. These findings demonstrate that genetic background and dose modulate ketamine sensitivity during adolescence.