Y decreasedEffects of SR 57227 and ondansetron on mortality in PTZ-treated miceIn the mortality studies, we observed one hundred mortality in mice with PTZ (90 mg/kg, i.p.) alone inside 30 min. Animals died as a direct result with the intervention. Mortality was monitored by video camera only for 6 h to minimize suffering in other groups. Mice with video monitoring were checked as soon as each and every 30 min. In table two the mortality induced by high-dose PTZ (90 mg/kg, i.p.) have been substantially inhibited by high-dose SR 57227 (ten mg/kg, i.p) and VPA (400 mg/kg, p.o.) but not ondansetron (0.2, 0.five and 1.0 mg/ kg, i.p.). Furthermore, the inhibitory effects of SR 57227 onPLOS One | plosone.orgFigure 2. Effects of ondansetron on SR 57227-induced prolonged seizure latency. PTZ: pentylenetetrazole (65 mg/kg, i.p.); SR 57227: 10 mg/kg, i.p; Ond: ondansetron (0.2 mg/kg, i.p.); VPA: sodium valproate (400 mg/kg, p.o.). Columns represent the mean six S.E.M. n = 8?0. ** P,0.01 vs PTZ group. doi:10.1371/journal.pone.0093158.gThe Anticonvulsant Effects on SeizureTable 1. Effects of SR 57227 and ondansetron on PTZinduced seizure score in mice.Table two. Effects of SR 57227 and ondansetron on PTZinduced mortality in mice.Treatment PTZ PTZ + SR (1 mg/kg) PTZ + SR (5 mg/kg) PTZ + SR (ten mg/kg) PTZ + Ond (0.2 mg/kg) PTZ + Ond (0.five mg/kg) PTZ + Ond (1 mg/kg) PTZ + SR (10 mg/kg) + Ond (0.2 mg/kg) PTZ + VPA (400 mg/kg)Seizure score 4.8560.14 four.2360.13 three.8260.43 2.0960.22* 4.8660.ten four.7760.15 4.8160.26 4.7560.32 1.4760.21*Treatment PTZ PTZ + SR (1 mg/kg) PTZ + SR (5 mg/kg) PTZ + SR (10 mg/kg) PTZ + Ond (0.two mg/kg) PTZ + Ond (0.5 mg/kg) PTZ + Ond (1 mg/kg) PTZ + SR (ten mg/kg) + Ond (0.two mg/kg) PTZ + VPA (400 mg/kg)Mortality Mortality 10/10 8/8 6/8 3/10** 9/10 8/9 8/10 8/9 2/9** 100 100 75 30 90 88.9 80 88.9 22.SR: SR 57227 (1, 5, and 10 mg/kg, i.p); PTZ: pentylenetetrazole (65 mg/kg, i.p); Ond: ondansetron (0.2, 0.5 and 1 mg/kg, i.p.). VPA: sodium valproate (400 mg/ kg, p.o.). n = eight?0 per group. * P,0.05, vs PTZ group. doi:ten.1371/journal.pone.0093158.tSR: SR 57227 (1, five, and ten mg/kg, i.p.); PTZ: pentylenetetrazole (90 mg/kg, i.p.); Ond: ondansetron (0.2, 0.Price of 1H-pyrrolo[2,3-c]pyridine-7-carbaldehyde 5 and 1 mg/kg, i.90725-49-8 Formula p.). VPA: sodium valproate (400 mg/ kg, p.o.). n = 8?0 per group. ** P,0.01 (Fisher’s exact test), vs PTZ group. doi:10.1371/journal.pone.0093158.tPTZ-induced c-Fos expression in these regions of hippocampus. On the other hand, the c-Fos expression was significantly inhibited by ondansetron in mice treated with SR 57227 and PTZ in comparison with the PTZ-treated group alone (P,0.001).Effects of SR 57227 and ondansetron on GABA levels in hippocampus and cortex of PTZ-treated miceFig.PMID:33499726 4 shows the effects of SR 57227 and ondansetron on GABA levels in hippocampus and cortex of PTZ-treated mice. GABA levels have been substantially inhibited by PTZ (65 mg/kg, i.p.) in each hippocampus and cortex (hippocampus, P,0.05; cortex, P,0.05). Furthermore, reduction of GABA levels was attenuated by SR 57227 in PTZ-treated mice (P,0.01). On the other hand, the effects of SR 57227 on GABA levels in hippocampus but not cortex had been blocked by ondansetron (0.two mg/kg, i.p.).DiscussionIn the present study seizure latency was substantially prolonged by acute SR 57227 inside a dose-dependent manner, along with the seizure score and mortality had been also decreased by SR 57227. Additionally, these anticonvulsant effects have been blocked by ondansetron. These findings suggest that activation of 5-HT3 receptor may play a crucial part on control of seizure induced by PTZ. However, preceding.