Figure 4

Ts65Dn and control mice display a similar dose-dependent susceptibility to picrotoxin-induced seizures, which can be effectively prevented by diazepam. (a) Video-EEG was recorded from control and Ts65Dn mice that were i.p. injected with picrotoxin at 2- (control, N = 14; Ts65Dn, N = 15) and 4-mg/kg doses (control, N = 11; Ts65Dn, N = 14). The experiment consisted of a 30-min baseline recording, followed by a 90-min post-dosing recording. (b) The administration of 2 mg/kg picrotoxin evoked convulsive seizures (CS) in approximately 64% and 47% of control and Ts65Dn mice, respectively. All mice of both genotypes exhibited CS when treated with 4 mg/kg picrotoxin. (c, d) Picrotoxin produced a dose-dependent effect on seizure severity score (c) and latency for CS onset (d) in both control and Ts65Dn mice, the highest dosage of picrotoxin (4 mg/kg) induced more severe seizures within a shorter period of time. (e) Survival curves for control and Ts65Dn mice treated with 4 mg/kg picrotoxin were not significantly different. (f) We then acutely pretreated control and Ts65Dn mice with 3 mg/kg diazepam (i.p.) before seizure-induction by 2 mg/kg picrotoxin. The experiment consisted of a 30-min baseline recording, followed by a 30-min post-dosing recording immediately after mice received an i.p. injection of 3 mg/kg diazepam. Mice were then injected with 2 mg/kg picrotoxin (i.p.) and recordings continued for an additional 60 min. (g) Both control and Ts65Dn pretreated with 3 mg/kg diazepam (PT) showed a decrease in the severity of picrotoxin-induced seizures compared with their respective non-pretreated peers (NPT). (h) Diazepam at 3-mg/kg dose almost completely prevented the occurrence of CS in both control and Ts65Dn mice (only one PT mice of each genotype developed CS). Number of mice: Ct 2 mg/kg PTX (N = 14), Ct 4 mg/kg PTX (N = 11), Ct non-pretreated with 3 mg/kg diazepam (NPT; N = 14), Ct pretreated with 3 mg/kg diazepam (PT; N = 12), Ts 2 mg/kg PTX (N = 15), Ts 4 mg/kg PTX (N = 14), Ts non-pretreated with 3 mg/kg diazepam (NPT; N = 15), and Ts pretreated with 3 mg/kg diazepam (PT; N = 15). Data represent mean ± SEM. Statistical significance is expressed as *, ** and *** for P < 0.05, P < 0.01, and P < 0.001, respectively.