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. Author manuscript; available in PMC: 2013 Sep 6.

Published in final edited form as: Neuroscience. 2012 May 18;219:33–47. doi: 10.1016/j.neuroscience.2012.05.003

Rapamycin increases seizure susceptibility to pilocarpine in immature rats. Immature rats were treated with rapamycin (labeled as Rap) or vehicle for 3 days prior to induction of seizures by pilocarpine at 300 mg/kg (labeled as P300) (A–C) or 255 mg/kg (labeled as P255) (D–F). Behavioral seizures induced by pilocarpine at 300 mg/kg are presented as average seizure duration (min) (pilocarpine: 3.87 ± 0.94 vs rapamycin/pilocarpine: 7.05 ± 1.10) (A), average seizure scale (pilocarpine: 2.36 ± 0.30 vs rapamycin/pilocarpine: 3.25 ± 1.81) (B), and average number of stage 4 and 5 seizures (pilocarpine: 2.33 ± 0.97 vs rapamycin/pilocarpine: 5.44 ± 1.08) (C). Behavioral seizures induced by pilocarpine at 255 mg/kg are presented as average seizure duration (min) (pilocarpine: 0.04 ± 0.02 vs rapamycin/pilocarpine: 7.98 ± 1.53) (D), average seizure scale (pilocarpine: 0.18 ± 0.10 vs rapamycin/pilocarpine: 2.07 ± 0.26) (E), and average number of stage 4 and 5 seizures (pilocarpine: 0 ± 0 vs rapamycin/pilocarpine: 2.67 ± 0.76) (F). (mean ± SEM; n=10–12; *<0.05; t-test). Typical electrographic seizures recorded from cortex in immature rats that were treated with pilocarpine at 255 mg/kg (G) or rapamycin plus pilocarpine at 255 mg/kg (H). Quantification of electrographic seizures presented as total seizure duration (min) (pilocarpine: 20.9 ± 9.4 vs rapamycin/pilocarpine: 52.7 ± 6.0) (I), average of total SE duration (min) (pilocarpine: 18.0 ± 8.5 vs rapamycin/pilocarpine: 50.2 ± 5.0) (J), and latency to onset of seizures (min) (pilocarpine: 38.6 ± 9.3 vs rapamycin/pilocarpine: 13.9 ± 2.8) (K). (mean ± SEM; n=7–8; *<0.05; t-test). Pilocapine elicited higher mortality in the rapamycin-treated group (L). Rats (3–4 weeks old) were treated with 5 mg/kg rapamycin or vehicle for 3 days prior to induction of SE by pilocarpine at 255 mg/kg. Seizures were terminated with sodium pentobarbital (25 mg/kg, i.p.) 60 min after pilocarpine administration. Mortality rates (%) were calculated within 16 hr after pilocarpine treatment (pilocarpine: 0.1563 ± 0.0146 vs. rapamycin/pilocarpine: 23.7798 ± 3.8091). (mean ± SEM; n=49–50; t-test, * indicates p<0.05, ** indicates p<0.01). Single dose of rapamycin does not significantly change seizure susceptibility to pilocarpine in immature rats (M–O). Immature rats were treated with 5 mg/kg rapamycin or vehicle 1 day (16 hr) prior to induction of seizures by pilocarpine at 255 mg/kg. Behavioral seizures induced by pilocarpine are presented as average seizure duration (min) (pilocarpine: 0.9600 ± 0.1815 vs rapamycin/pilocarpine: 1.3783 ± 0.4588) (A), average seizure scale (pilocarpine: 0.35 ± 0.0825 vs rapamycin/pilocarpine: 0.94 ± 0.3365) (B) and average number of stage 4 and 5 seizures (pilocarpine: 0.33 ± 0.1925 vs. rapamycin/pilocarpine: 0.500 ± 0.2041) (mean ± SEM; n=6; t-test).

Rapamycin increases seizure susceptibility to pilocarpine in immature rats. Immature rats were treated with rapamycin (labeled as Rap) or vehicle for 3 days prior to induction of seizures by pilocarpine at 300 mg/kg (labeled as P300) (A–C) or 255 mg/kg (labeled as P255) (D–F). Behavioral seizures induced by pilocarpine at 300 mg/kg are presented as average seizure duration (min) (pilocarpine: 3.87 ± 0.94 vs rapamycin/pilocarpine: 7.05 ± 1.10) (A), average seizure scale (pilocarpine: 2.36 ± 0.30 vs rapamycin/pilocarpine: 3.25 ± 1.81) (B), and average number of stage 4 and 5 seizures (pilocarpine: 2.33 ± 0.97 vs rapamycin/pilocarpine: 5.44 ± 1.08) (C). Behavioral seizures induced by pilocarpine at 255 mg/kg are presented as average seizure duration (min) (pilocarpine: 0.04 ± 0.02 vs rapamycin/pilocarpine: 7.98 ± 1.53) (D), average seizure scale (pilocarpine: 0.18 ± 0.10 vs rapamycin/pilocarpine: 2.07 ± 0.26) (E), and average number of stage 4 and 5 seizures (pilocarpine: 0 ± 0 vs rapamycin/pilocarpine: 2.67 ± 0.76) (F). (mean ± SEM; n=10–12; *<0.05; t-test). Typical electrographic seizures recorded from cortex in immature rats that were treated with pilocarpine at 255 mg/kg (G) or rapamycin plus pilocarpine at 255 mg/kg (H). Quantification of electrographic seizures presented as total seizure duration (min) (pilocarpine: 20.9 ± 9.4 vs rapamycin/pilocarpine: 52.7 ± 6.0) (I), average of total SE duration (min) (pilocarpine: 18.0 ± 8.5 vs rapamycin/pilocarpine: 50.2 ± 5.0) (J), and latency to onset of seizures (min) (pilocarpine: 38.6 ± 9.3 vs rapamycin/pilocarpine: 13.9 ± 2.8) (K). (mean ± SEM; n=7–8; *<0.05; t-test). Pilocapine elicited higher mortality in the rapamycin-treated group (L). Rats (3–4 weeks old) were treated with 5 mg/kg rapamycin or vehicle for 3 days prior to induction of SE by pilocarpine at 255 mg/kg. Seizures were terminated with sodium pentobarbital (25 mg/kg, i.p.) 60 min after pilocarpine administration. Mortality rates (%) were calculated within 16 hr after pilocarpine treatment (pilocarpine: 0.1563 ± 0.0146 vs. rapamycin/pilocarpine: 23.7798 ± 3.8091). (mean ± SEM; n=49–50; t-test, * indicates p<0.05, ** indicates p<0.01). Single dose of rapamycin does not significantly change seizure susceptibility to pilocarpine in immature rats (M–O). Immature rats were treated with 5 mg/kg rapamycin or vehicle 1 day (16 hr) prior to induction of seizures by pilocarpine at 255 mg/kg. Behavioral seizures induced by pilocarpine are presented as average seizure duration (min) (pilocarpine: 0.9600 ± 0.1815 vs rapamycin/pilocarpine: 1.3783 ± 0.4588) (A), average seizure scale (pilocarpine: 0.35 ± 0.0825 vs rapamycin/pilocarpine: 0.94 ± 0.3365) (B) and average number of stage 4 and 5 seizures (pilocarpine: 0.33 ± 0.1925 vs. rapamycin/pilocarpine: 0.500 ± 0.2041) (mean ± SEM; n=6; t-test).