Extended Data Fig. 10: Evaluation of the safety profile of Lys05 in vivo.
From: Pharmacological inhibition of Kir4.1 evokes rapid-onset antidepressant responses
a, Schematics showing the experimental design. Mice were treated with a single dose (10 or 30 mg/kg, 0.5 h ahead) or multiple doses (30 mg/kg per dose, once daily for 5 days) of Lys05 and assigned to behavioral assessments. b, Seizure susceptibility of mice treated with a single injection (n = 6-8 mice per stimulus intensity per group) of Lys05 at the indicated doses in the 6-Hz seizure test. Left, CS50 (Vehicle) = 18.1 (16.8-19.4) mA; CS50 (10 mg/kg Lys05) = 18.0 (17.1-18.8) mA; Right, CS50 (Vehicle) = 16.9 (15.5-18.6) mA; CS50 (30 mg/kg Lys05) = 19.1 (18.3-19.8) mA. c, Mice treated with multiple injections in the same assay (n = 4-7 mice per stimulus intensity per group). CS50 (Vehicle)= 15.3 (11.5-20.5) mA; CS50 (Lys05) = 15.8 (13.1-19.0) mA. d, Seizure susceptibility of mice treated with a single dose (n = 6-8 mice per stimulus intensity per group) of Lys05 as indicated in the MES test. Left, CS50 (Vehicle) = 0.68 (0.62-0.74) mA; CS50 (10 mg/kg Lys05) = 0.67 (0.65-0.69) mA. Right, CS50 (Vehicle) = 0.69 (0.60-0.76) mA; CS50 (30 mg/kg Lys05) = 0.75 (0.60-0.80) mA. e, Mice treated with multiple injections in the same assay (n = 4-7 mice per stimulus intensity per group). CS50 (Vehicle) = 0.65 (0.59-0.70) mA; CS50 (Lys05) = 0.67 (0.64-0.71) mA. f, Effects of Lys05 treatment at indicated doses on motor coordination in the rotarod test (n = 10-25 mice per group). Data are percentage of mice with seizure manifestations in b-e and N/T values illustrated in f.
