The Anticonvulsant Effects of SR 57227 on Pentylenetetrazole-Induced Seizure in Mice

Recently, studies have shown that serotonin plays an important role in the control of seizure. However, the specific role of 5-HT receptor subtypes is not yet well described, in particular that of the 5-HT(3) receptor. The present study was aimed to investigate the role of 5-HT(3) receptor on the pentylenetetrazole (PTZ)-induced seizure in mice. Firstly, seizure latency was significantly prolonged by a 5-HT(3) receptor agonist SR 57227 in a dose-dependent manner. Seizure score and mortality were also decreased by SR 57227 in PTZ-treated mice. Furthermore, these anticonvulsant effects of SR 57227 were inhibited by a 5-HT(3) receptor antagonist ondansetron. However, ondansetron alone had no effect on seizure latency, seizure score or mortality at different doses. Immunohistochemical studies have also shown that c-Fos expression was significantly increased in hippocampus (dentate gyrus, CA1, CA3 and CA4) of PTZ-treated mice. Furthermore, c-Fos expression was significantly inhibited by ondansetron in mice treated with PTZ and SR 57227. An ELISA study showed that SR 57227 attenuated the PTZ-induced inhibitory effects of GABA levels in hippocampus and cortex, and the attenuated effects of SR 57227 were antagonized by ondansetron in hippocampus but not cortex. Our findings suggest that activation of 5-HT(3) receptor by SR 57227, which plays an important role on the control of seizure induced by PTZ, may be related to GABA activity in hippocampus. Therefore, 5-HT(3) receptor subtype is a potential target for the treatment of epilepsy.